Skip to main content
SpringerLink
Log in

Structure and Function of SNM1 Family Nucleases

  • Chapter
  • First Online:
Protein Reviews

Part of the book series: Advances in Experimental Medicine and Biology ((PROTRE,volume 1414))

Abstract

Three human nucleases, SNM1A, SNM1B/Apollo, and SNM1C/Artemis, belong to the SNM1 gene family. These nucleases are involved in various cellular functions, including homologous recombination, nonhomologous end-joining, cell cycle regulation, and telomere maintenance. These three proteins share a similar catalytic domain, which is characterized as a fused metallo-β-lactamase and a CPSF-Artemis-SNM1-PSO2 domain. SNM1A and SNM1B/Apollo are exonucleases, whereas SNM1C/Artemis is an endonuclease. This review contains a summary of recent research on SNM1’s cellular and biochemical functions, as well as structural biology studies. In addition, protein structure prediction by the artificial intelligence program AlphaFold provides a different view of the proteins’ non-catalytic domain features, which may be used in combination with current results from X-ray crystallography and cryo-EM to understand their mechanism more clearly.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

53BP1:

p53-binding protein

ATM:

Ataxia telangiectasia mutated

CHFR:

Checkpoint with forkhead and ring finger

Co-IP:

Co-immunoprecipitation

CSB:

Cockayne syndrome group B

DBD:

DNA binding domain

DCLRE:

DNA crosslink repair

DNA-PKcs:

DNA-dependent protein kinase catalytic subunit

DSB:

DNA double-strand break

FA:

Fanconi anemia

HR:

Homologous recombination

ICL:

DNA interstrand crosslinks

IR:

Ionizing radiation

MBL:

Metallo-β-lactamase

MMC:

Mitomycin C

MRN complex:

A complex of Mre11, Rad50, and Nbs1

NHEJ:

Nonhomologous end-joining

PAR:

Poly(ADP-ribose)

PBZ:

PAR-binding zinc finger

PCNA:

Proliferating cell nuclear antigen

PDB:

Protein data bank

PIP box:

PCNA-interacting protein box

SCID:

Severe combined immunodeficiency

SNM1 :

Sensitive to nitrogen mustard 1

TRF:

Telomeric repeat-binding factor

UBZ:

Ubiquitin-binding zinc finger

V(D)J recombination:

Variable (V), diversity (D), and joining (J) recombination

β-CASP :

Metallo-β-lactamase-associated CPSF Artemis SNM1/PSO2

References

  • Ahkter S, Richie CT, Zhang N, Behringer RR, Zhu C, Legerski RJ (2005) Snm1-deficient mice exhibit accelerated tumorigenesis and susceptibility to infection. Mol Cell Biol 25:10071–10078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Akhter S, Legerski RJ (2008) SNM1A acts downstream of ATM to promote the G1 cell cycle checkpoint. Biochem Biophys Res Commun 377:236–241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Akhter S, Richie CT, Deng JM, Brey E, Zhang X, Patrick C, Behringer RR, Legerski RJ (2004) Deficiency in SNM1 abolishes an early mitotic checkpoint induced by spindle stress. Mol Cell Biol 24:10448–10455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Allerston CK, Lee SY, Newman JA, Schofield CJ, Mchugh PJ, Gileadi O (2015) The structures of the SNM1A and SNM1B/Apollo nuclease domains reveal a potential basis for their distinct DNA processing activities. Nucleic Acids Res 43:11047–11060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anderson L, Henderson C, Adachi Y (2001) Phosphorylation and rapid relocalization of 53BP1 to nuclear foci upon DNA damage. Mol Cell Biol 21:1719–1729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andrews AM, McCartney HJ, Errington TM, D’Andrea AD, Macara IG (2018) A senataxin-associated exonuclease SAN1 is required for resistance to DNA interstrand cross-links. Nat Commun 9:2592

    Article  PubMed  PubMed Central  Google Scholar 

  • Anne Esguerra Z, Watanabe G, Okitsu CY, Hsieh CL, Lieber MR (2020) DNA-PKcs chemical inhibition versus genetic mutation: impact on the junctional repair steps of V(D)J recombination. Mol Immunol 120:93–100

    Article  CAS  PubMed  Google Scholar 

  • Aravind L (1999) An evolutionary classification of the metallo-beta-lactamase fold proteins. In Silico Biol 1:69–91

    CAS  PubMed  Google Scholar 

  • Baddock HT, Yosaatmadja Y, Newman JA, Schofield CJ, Gileadi O, McHugh PJ (2020) The SNM1A DNA repair nuclease. DNA Repair (Amst) 95:102941

    Article  CAS  PubMed  Google Scholar 

  • Baddock HT, Newman JA, Yosaatmadja Y, Bielinski M, Schofield CJ, Gileadi O, McHugh PJ (2021) A phosphate binding pocket is a key determinant of exo- versus endo-nucleolytic activity in the SNM1 nuclease family. Nucleic Acids Res 49:9294–9309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bae JB, Mukhopadhyay SS, Liu L, Zhang N, Tan J, Akhter S, Liu X, Shen X, Li L, Legerski RJ (2008) Snm1B/Apollo mediates replication fork collapse and S phase checkpoint activation in response to DNA interstrand cross-links. Oncogene 27:5045–5056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barnum KJ, O’Connell MJ (2014) Chapter 2 cell cycle regulation by checkpoints. Methods Mol. Biol 1170:29–40

    Article  PubMed  PubMed Central  Google Scholar 

  • Batenburg NL, Thompson EL, Hendrickson EA, Zhu X (2015) Cockayne syndrome group B protein regulates DNA double-strand break repair and checkpoint activation. EMBO J 34:1399–1416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berney M, Doherty W, Jauslin WT, Manoj T, Dürr EM, McGouran JF (2021) Synthesis and evaluation of squaramide and thiosquaramide inhibitors of the DNA repair enzyme SNM1A. Bioorganic Med Chem 46:116369

    Article  CAS  Google Scholar 

  • Bomar MG, Pai MT, Tzeng SR, Li SSC, Zhou P (2007) Structure of the ubiquitin-binding zinc finger domain of human DNA Y-polymerase η. EMBO Rep 8:247–251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonomo RA (2017) β-Lactamases: a focus on current challenges. Cold Spring Harb Perspect Med 7:a025239

    Article  PubMed  PubMed Central  Google Scholar 

  • Brandsma I, Van Gent DC (2012) Pathway choice in DNA double strand break repair: observations of a balancing act. Genome Integr 3:9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brünger AT (1992) Free R value: a novel statistical quantity for assessing the accuracy of crystal structures. Nature 355:472–475

    Article  PubMed  Google Scholar 

  • Bush K, Jacoby GA, Medeiros AA (1995) A functional classification scheme for-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother 39:1211–1233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buzon B, Grainger R, Huang S, Rzadki C, Junop MS (2018) Structure-specific endonuclease activity of SNM1A enables processing of a DNA interstrand crosslink. Nucleic Acids Res 46:9057–9066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buzon B, Grainger RA, Rzadki C, Huang SYM, Junop M (2021) Identification of bioactive SNM1A inhibitors. ACS Omega 6:9352–9361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Callebaut I, Moshous D, Mornon J-P, De Villartay J-P (2002) Metallo-b-lactamase fold within nucleic acids processing enzymes: the b-CASP family. Nucleic Acids Res 30:3592–3601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cannan WJ, Pederson DS (2016) Mechanisms and consequences of double-strand DNA break formation in chromatin. J Cell Physiol 231:3–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cassier-Chauvat C, Moustacchi E (1988) Allelism between pso1-1 and rev3-1 mutants and between pso2-1 and snm1 mutants in saccharomyces cerevisiaee. Curr Genet 13:37–40

    Article  CAS  PubMed  Google Scholar 

  • Cattell E, Sengerová B, McHugh PJ (2010) The SNM1/Pso2 family of ICL repair nucleases: from yeast to man. Environ Mol Mutagen 51:635–645

    CAS  PubMed  Google Scholar 

  • Chang HHY, Pannunzio NR, Adachi N, Lieber MR (2017) Non-homologous DNA end joining and alternative pathways to double-strand break repair. Nat Rev Mol Cell Biol 18:495–506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen Y, Yang Y, van Overbeek M, Donigian JR, Baciu P, de Lange T, Lei M (2008) A shared docking motif in TRF1 and TRF2 used for differential recruitment of telomeric proteins. Science 319:1092–1096

    Article  CAS  PubMed  Google Scholar 

  • Coppedè F, Migliore L (2015) DNA damage in neurodegenerative diseases. Mutat Res Mol Mech Mutagen 776:84–97

    Article  Google Scholar 

  • Dai Y, Kysela B, Hanakahi LA, Manolis K, Riballo E, Stumm M, Harville TO, West SC, Oettinger MA, Jeggo PA et al (2003) Nonhomologous end joining and V(D)J recombination require an additional factor. Proc Natl Acad Sci 100:2462–2467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daiyasu H, Osaka K, Ishino Y, Toh H (2001) Expansion of the zinc metallo-hydrolase family of the L-lactamase fold. FEBS 503:1–6

    Article  CAS  Google Scholar 

  • Darroudi F, Wiegant W, Meijers M, Friedl AA, van der Burg M, Fomina J, van Dongen JJM, van Gent DC, Zdzienicka MZ (2007) Role of Artemis in DSB repair and guarding chromosomal stability following exposure to ionizing radiation at different stages of cell cycle. Mutat Res 615:111–124

    Article  CAS  PubMed  Google Scholar 

  • Dasari S, Bernard Tchounwou P (2014) Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 740:364–378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De P, Peak MM, Rodgers KK (2004) DNA cleavage activity of the V(D)J recombination protein RAG1 is autoregulated. Mol Cell Biol 24:6850–6860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Ioannes P, Malu S, Cortes P, Aggarwal AK (2012) Structural basis of DNA ligase IV-Artemis interaction in nonhomologous end-joining. Cell Rep 2:1505–1512

    Article  PubMed  PubMed Central  Google Scholar 

  • De Lange T (2005) Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 19:2100–2110

    Article  PubMed  Google Scholar 

  • de Villartay J-P, Shimazaki N, Charbonnier J-B, Fischer A, Mornon J-P, Lieber MR, Callebaut I (2009) A histidine in the beta-CASP domain of Artemis is critical for its full in vitro and in vivo functions. DNA Repair (Amst) 8:202–208

    Article  PubMed  Google Scholar 

  • Dominski Z (2007) Nucleases of the metallo-β-lactamase family and their role in DNA and RNA metabolism. Crit Rev Biochem Mol Biol 42:67–93

    Article  CAS  PubMed  Google Scholar 

  • Dronkert MLG, De Wit J, Boeve M, Luisa Vasconcelos M, Van Steeg H, Tan TLR, Hoeijmakers JHJ, Kanaar R (2000) Disruption of mouse SNM1 causes increased sensitivity to the DNA interstrand cross-linking agent mitomycin C. Mol Cell Biol 20:4553–4561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dudásová Z, Chovanec M (2003) Artemis, a novel guardian of the genome. Neoplasma 50:311–318

    PubMed  Google Scholar 

  • Dvorak CC, Cowan MJ (2010) Radiosensitive severe combined immunodeficiency disease. Immunol Allergy Clin N Am 30:125–142

    Article  Google Scholar 

  • Ege M, Ma Y, Manfras B, Kalwak K, Lu H, Lieber MR, Schwarz K, Pannicke U (2005) Omenn syndrome due to ARTEMIS mutations. Blood 105:4179–4186

    Article  CAS  PubMed  Google Scholar 

  • Evans PM, Woodbine L, Riballo E, Gennery AR, Hubank M, Jeggo PA (2006) Radiation-induced delayed cell death in a hypomorphic Artemis cell line. Hum Mol Genet 15:1303–1311

    Article  CAS  PubMed  Google Scholar 

  • Fang CB, Wu HT, Zhang ML, Liu J, Zhang GJ (2020) Fanconi Anemia pathway: mechanisms of breast cancer predisposition development and potential therapeutic targets. Front Cell Dev Biol 8:160

    Article  PubMed  PubMed Central  Google Scholar 

  • Felgentreff K, Lee YN, Frugoni F, Du L, Van Der Burg M, Giliani S, Tezcan I, Reisli I, Mejstrikova E, De Villartay JP et al (2015) Functional analysis of naturally occurring DCLRE1C mutations and correlation with the clinical phenotype of ARTEMIS deficiency. J Allergy Clin Immunol 136:140–150.e7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fleming A (1929) On the antibacterial action of cultures of a Penicillium, with special reference to their use in the isolation of B. influenzæ. Br J Exp Pathol 10:226–236

    CAS  PubMed Central  Google Scholar 

  • Freibaum BD, Counter CM (2006) hSnm1B is a novel telomere-associated protein. J Biol Chem 281:15033–15036

    Article  CAS  PubMed  Google Scholar 

  • Freitas AA, De Magalhães JP (2011) A review and appraisal of the DNA damage theory of ageing. Mutat Res Mutat Res 728:12–22

    Article  CAS  PubMed  Google Scholar 

  • Garau G, García-Sáez I, Bebrone C, Anne C, Mercuri P, Galleni M, Frère JM, Dideberg O (2004) Update of the standard numbering scheme for class B β-lactamases. Antimicrob Agents Chemother 48:2347–2349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gerodimos CA, Chang HHY, Watanabe G, Lieber MR (2017) Effects of DNA end configuration on XRCC4-DNA ligase IV and its stimulation of Artemis activity. J Biol Chem 292:13914–13924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldberg FW, Raymond M, Finlay V, Ting AKT, Beattie D, Lamont GM, Fallan C, Wrigley GL, Schimpl M, Howard MR et al (2020) The discovery of 7-methyl-2-[(7-methyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino]-9-(tetrahydro-2H-pyran-4-yl)-7,9-dihydro-8H-purin-8-one (AZD7648), a potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor. J Med Chem 63:3461–3471

    Article  CAS  PubMed  Google Scholar 

  • Goodarzi AA, Yu Y, Riballo E, Douglas P, Walker SA, Ye R, Härer C, Marchetti C, Morrice N, Jeggo PA et al (2006) DNA-PK autophosphorylation facilitates Artemis endonuclease activity. EMBO J 25:3880–3889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harnor SJ, Lfie Brennan A, Cano C (2017) Targeting DNA-dependent protein kinase for cancer therapy. ChemMedChem 12:895–900

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto S, Anai H, Hanada K (2016) Mechanisms of interstrand DNA crosslink repair and human disorders. Genes Environ 38:9

    Article  PubMed  PubMed Central  Google Scholar 

  • Hejna J, Philip S, Ott J, Faulkner C, Moses R (2007) The hSNM1 protein is a DNA 5′-exonuclease. Nucleic Acids Res 35:6115–6123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hemphill AW, Bruun D, Thrun L, Akkari Y, Torimaru Y, Hejna K, Jakobs PM, Hejna J, Jones S, Olson SB et al (2008) Mammalian SNM1 is required for genome stability. Mol Genet Metab 94:38–45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hognon C, Monari A (2021) Staring at the naked goddess. Unraveling structure and reactivity of Artemis endonuclease interacting with a DNA double. Molecules 26:3986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang Y, Li L (2013) DNA crosslinking damage and cancer – a tale of friend and foe. Transl Cancer Res 2:144–154

    CAS  PubMed  Google Scholar 

  • Iyama T, Lee SY, Berquist BR, Gileadi O, Bohr VA, Seidman MM, McHugh PJ, Wilson DM (2015) CSB interacts with SNM1A and promotes DNA interstrand crosslink processing. Nucleic Acids Res 43:247–258

    Article  CAS  PubMed  Google Scholar 

  • Jackson SP, Bartek J (2009) The DNA-damage response in human biology and disease. Nature 461:1071–1078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jafri MA, Ansari SA, Alqahtani MH, Shay JW (2016) Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies. Genome Med 8:69

    Article  PubMed  PubMed Central  Google Scholar 

  • Jamieson ER, Lippard SJ (1999) Structure, recognition, and processing of cisplatin−DNA adducts. Chem Rev 99:2467–2498

    Article  CAS  PubMed  Google Scholar 

  • Jowsey P, Morrice NA, Hastie CJ, McLauchlan H, Toth R, Rouse J (2007) Characterisation of the sites of DNA damage-induced 53BP1 phosphorylation catalysed by ATM and ATR. DNA Repair (Amst) 6:1536–1544

    Article  CAS  PubMed  Google Scholar 

  • Jumper J, Evans R, Pritzel A, Green T, Figurnov M et al (2021) Highly accurate protein structure prediction with AlphaFold. Nature 596:583–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karim MF, Liu S, Laciak AR, Volk L, Koszelak-Rosenblum M, Lieber MR, Wu M, Curtis R, Huang NN, Carr G et al (2020) Structural analysis of the catalytic domain of Artemis endonuclease/SNM1C reveals distinct structural features. J Biol Chem 295:12368–12377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kelman Z (1997) PCNA: structure, functions and interactions. Oncogene 14:629–640

    Article  CAS  PubMed  Google Scholar 

  • Kim H, D’Andrea AD (2012) Regulation of DNA cross-link repair by the Fanconi anemia/BRCA pathway. Genes Dev 26:1393–1408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim M-S, Lapkouski M, Yang W, Gellert M (2015) Crystal structure of the V(D)J recombinase RAG1-RAG2. Nature 518:507–511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klein Douwel D, Boonen RACM, Long DT, Szypowska AA, Räschle M, Walter JC, Knipscheer P (2014) XPF-ERCC1 acts in unhooking DNA interstrand crosslinks in cooperation with FANCD2 and FANCP/SLX4. Mol Cell 54:460–471

    Article  CAS  PubMed  Google Scholar 

  • Krokan HE, Bjørås M (2013) Base excision repair. Cold Spring Harb Perspect Biol 5:1–22

    Article  Google Scholar 

  • Lam YC, Akhter S, Gu P, Ye J, Poulet A, Giraud-Panis MJ, Bailey SM, Gilson E, Legerski RJ, Chang S (2010) SNMIB/Apollo protects leading-strand telomeres against NHEJ-mediated repair. EMBO J 29:2230–2241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lamarche BJ, Orazio NI, Weitzman MD (2010) The MRN complex in double-strand break repair and telomere maintenance. FEBS Lett 584:3682–3695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • LaMarche MJ, Acker M, Argintaru A, Bauer D, Boisclair J, Chan H, Chen CH-T, Chen Y-N, Chen Z, Deng Z et al (2020) Identification of TNO155, an allosteric SHP2 inhibitor for the treatment of cancer. J Med Chem 63:13578–13594

    Article  CAS  PubMed  Google Scholar 

  • Lee SY, Brem J, Pettinati I, Claridge TDW, Gileadi O, Schofield CJ, McHugh PJ (2016) Cephalosporins inhibit human metallo β-lactamase fold DNA repair nucleases SNM1A and SNM1B/apollo. Chem Commun 52:6727–6730

    Article  CAS  Google Scholar 

  • Lee L, Belen Perez Oliva A, Martinez-Balsalobre E, Churikov D, Peter J, Rahmouni D, Audoly G, Azzoni V, Audebert S, Camoin L et al (2021) UFMylation of MRE11 is essential for telomere length maintenance and hematopoietic stem cell survival. Sci Adv 7:7371–7395

    Article  Google Scholar 

  • Lenain C, Bauwens S, Amiard S, Brunori M, Giraud-Panis MJ, Gilson E (2006) The Apollo 5′ exonuclease functions together with TRF2 to protect telomeres from DNA repair. Curr Biol 16:1303–1310

    Article  CAS  PubMed  Google Scholar 

  • Li GM (2008) Mechanisms and functions of DNA mismatch repair. Cell Res 18:85–98

    Article  CAS  PubMed  Google Scholar 

  • Li X, Heyer WD (2008) Homologous recombination in DNA repair and DNA damage tolerance. Cell Res 18:99–113

    Article  CAS  PubMed  Google Scholar 

  • Li J, Xu X (2016) DNA double-strand break repair: a tale of pathway choices. Acta Biochim Biophys Sin Shanghai 48:641–646

    Article  CAS  PubMed  Google Scholar 

  • Li L, Moshous D, Zhou Y, Wang J, Xie G, Salido E, Hu D, de Villartay J-P, Cowan MJ (2002) A founder mutation in Artemis, an SNM1-like protein, causes SCID in Athabascan-speaking native Americans. J Immunol 168:6323–6329

    Article  CAS  PubMed  Google Scholar 

  • Li S, Chang HH, Niewolik D, Hedrick MP, Pinkerton AB, Hassig CA, Schwarz K, Lieber MR (2014) Evidence that the DNA endonuclease ARTEMIS also has intrinsic 5′-exonuclease activity. J Biol Chem 289:7825–7834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lieber MR (2010) The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem 79:181–211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu L, Chen X, Li J, Wang H, Buehl CJ, Goff NJ, Meek K, Yang W, Gellert M (2022) Autophosphorylation transforms DNA-PK from protecting to processing DNA ends. Mol Cell 82:177–189.e4

    Article  CAS  PubMed  Google Scholar 

  • Ma Y, Pannicke U, Schwarz K, Lieber MR (2002) Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination. Cell 108:781–794

    Article  CAS  PubMed  Google Scholar 

  • Ma Y, Schwarz K, Lieber MR (2005) The Artemis: DNA-PKcs endonuclease cleaves DNA loops, flaps, and gaps. DNA Repair (Amst) 4:845–851

    Article  CAS  PubMed  Google Scholar 

  • Madabhushi R, Pan L, Tsai LH (2014) DNA damage and its links to neurodegeneration. Neuron 83:266–282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maiuri T, Suart CE, Hung CLK, Graham KJ, Barba Bazan CA, Truant R (2019) DNA damage repair in Huntington’s disease and other neurodegenerative diseases. Neurotherapeutics 16:948–956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malu S, De Ioannes P, Kozlov M, Greene M, Francis D, Hanna M, Pena J, Escalante CR, Kurosawa A, Erdjument-Bromage H et al (2012) Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA ligase IV and DNA-pkcs. J Exp Med 209:955–963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mandel CR, Kaneko S, Zhang H, Gebauer D, Vethantham V, Manley JL, Tong L (2006) Polyadenylation factor CPSF-73 is the pre-mRNA 3′-end-processing endonuclease. Nature 444:953–956

    Article  CAS  PubMed  Google Scholar 

  • Mansilla-Soto J, Cortes P (2003) VDJ recombination: Artemis and its in vivo role in hairpin opening. J Exp Med 197:543–547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maret W (2017) Zinc in cellular regulation: the nature and significance of “zinc signals”. Int J Mol Sci 18:2285

    Article  PubMed  PubMed Central  Google Scholar 

  • Marteijn JA, Lans H, Vermeulen W, Hoeijmakers JHJ (2014) Understanding nucleotide excision repair and its roles in cancer and ageing. Nat Rev Mol Cell Biol 15:465–481

    Article  CAS  PubMed  Google Scholar 

  • Mason JM, Sekiguchi JAM (2011) Snm1B/Apollo functions in the fanconi anemia pathway in response to DNA interstrand crosslinks. Hum Mol Genet 20:2549–2559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mavragani IV, Nikitaki Z, Kalospyros SA, Georgakilas AG (2019) Ionizing radiation and complex DNA damage: from prediction to detection challenges and biological significance. Cancers (Basel) 11:1789

    Article  CAS  PubMed  Google Scholar 

  • Mcnicholas S, Potterton E, Wilson KS, Noble MEM (2011) Biological crystallography presenting your structures: the CCP4mg molecular-graphics software. Acta Crystallogr D67:386–394

    Google Scholar 

  • Moldovan GL, Pfander B, Jentsch S (2007) PCNA, the maestro of the replication fork. Cell 129:665–679

    Article  CAS  PubMed  Google Scholar 

  • Moscariello M, Wieloch R, Kurosawa A, Li F, Adachi N, Mladenov E, Iliakis G (2015) Role for Artemis nuclease in the repair of radiation-induced DNA double strand breaks by alternative end joining. DNA Repair (Amst) 31:29–40

    Article  CAS  PubMed  Google Scholar 

  • Moshous D, Callebaut I, Gina De Chasseval R, Corneo B, Cavazzana-Calvo M, Oise F, Deist L, Tezcan I, Sanal O, Bertrand Y et al (2001) Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency. Cell 105:177–186

    Article  CAS  PubMed  Google Scholar 

  • Moshous D, Pannetier C, de Chasseval R, le Deist F, Cavazzana-Calvo M, Romana S, Macintyre E, Canioni D, Brousse N, Fischer A et al (2003) Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis. J Clin Invest 111:381–387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Niewolik D, Schwarz K (2022) Physical ARTEMIS: DNA-PKcs interaction is necessary for V(D)J recombination. Nucleic Acids Res 50:2096–2110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Niewolik D, Pannicke U, Lu H, Ma Y, Wang LCV, Kulesza P, Zandi E, Lieber MR, Schwarz K (2006) DNA-PKcs dependence of Artemis endonucleolytic activity, differences between hairpins and 5′ or 3′ overhangs. J Biol Chem 281:33900–33909

    Article  CAS  PubMed  Google Scholar 

  • Niewolik D, Peter I, Butscher C, Schwarz K (2017) Autoinhibition of the nuclease ARTEMIS is mediated by a physical interaction between its catalytic and C-terminal domains. J Biol Chem 292:3351–3365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oberoi J, Richards MW, Crumpler S, Brown N, Blagg J, Bayliss R (2010) Structural basis of poly(ADP-ribose) recognition by the multizinc binding domain of checkpoint with Forkhead-associated and RING domains (CHFR). J Biol Chem 285:39348–39358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ou H-L, Schumacher B (2018) DNA damage responses and p53 in the aging process. Blood 131:488–495

    Article  CAS  PubMed  Google Scholar 

  • Pannicke U, Ma Y, Hopfner KP, Niewolik D, Lieber MR, Schwarz K (2004) Functional and biochemical dissection of the structure-specific nuclease ARTEMIS. EMBO J 23:1987–1997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pannicke U, Hönig M, Schulze I, Rohr J, Heinz GA, Braun S, Janz I, Rump E-M, Seidel MG, Matthes-Martin S et al (2010) The most frequent DCLRE1C (ARTEMIS) mutations are based on homologous recombination events. Hum Mutat 31:197–207

    Article  CAS  PubMed  Google Scholar 

  • Perera ON, Sobinoff AP, Teber ET, Harman A, Maritz MF, Yang SF, Pickett HA, Cesare AJ, Arthur JW, Mackenzie KL et al (2019) Telomerase promotes formation of a telomere protective complex in cancer cells. Sci Adv 5:eaav4409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Porro A, Berti M, Pizzolato J, Bologna S, Kaden S, Saxer A, Ma Y, Nagasawa K, Sartori AA, Jiricny J (2017) FAN1 interaction with ubiquitylated PCNA alleviates replication stress and preserves genomic integrity independently of BRCA2. Nat Commun 8:1073

    Article  PubMed  PubMed Central  Google Scholar 

  • Prestel A, Wichmann N, Martins JM, Marabini R, Kassem N, Broendum SS, Otterlei M, Nielsen O, Willemoës M, Ploug M et al (2019) The PCNA interaction motifs revisited: thinking outside the PIP-box. Cell Mol Life Sci 76:4923–4943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Räschle M, Knipsheer P, Enoiu M, Angelov T, Sun J, Griffith JD, Ellenberger TE, Schärer OD, Walter JC (2008) Mechanism of replication-coupled DNA interstrand crosslink repair. Cell 134:969–980

    Article  PubMed  PubMed Central  Google Scholar 

  • Richie CT, Peterson C, Lu T, Hittelman WN, Carpenter PB, Legerski RJ (2002) hSnm1 colocalizes and physically associates with 53BP1 before and after DNA damage. Mol Cell Biol 22:8635–8647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rohleder F, Huang J, Xue Y, Kuper J, Round A, Seidman M, Wang W, Kisker C (2016) FANCM interacts with PCNA to promote replication traverse of DNA interstrand crosslinks. Nucleic Acids Res 44:3219–3232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salewsky B, Schmiester M, Schindler D, Digweed M, Demuth I (2012) The nuclease hSNM1B/Apollo is linked to the Fanconi anemia pathway via its interaction with FANCP/SLX4. Hum Mol Genet 21:4948–4956

    Article  CAS  PubMed  Google Scholar 

  • Sasatani M, Xu Y, Kawai H, Cao L, Tateishi S, Shimura T, Li J, Iizuka D, Noda A, Hamasaki K et al (2015) RAD18 activates the G2/M checkpoint through DNA damage Signaling to maintain genome integrity after ionizing radiation exposure. PLoS One 10(2):e0117845

    Article  PubMed  PubMed Central  Google Scholar 

  • Schafer KA (1998) The cell cycle: a review. Vet Pathol 35:461–478

    Article  CAS  PubMed  Google Scholar 

  • Schärer OD (2013) Nucleotide excision repair in eukaryotes. Cold Spring Harb Perspect Biol 5:a012609

    Article  PubMed  PubMed Central  Google Scholar 

  • Schmiester M, Demuth I (2017) SNM1B/Apollo in the DNA damage response and telomere maintenance. Oncotarget 8:48398–48409

    Article  PubMed  PubMed Central  Google Scholar 

  • Sengerová B, Wang AT, McHugh PJ (2011) Orchestrating the nucleases involved in DNA interstrand cross-link (ICL) repair. Cell Cycle 10:3999–4008

    Article  PubMed  PubMed Central  Google Scholar 

  • Sengerová B, Allerston CK, Abu M, Lee SY, Hartley J, Kiakos K, Schofield CJ, Hartley JA, Gileadi O, McHugh PJ (2012) Characterization of the human SNM1A and SNM1B/Apollo DNA repair exonucleases. J Biol Chem 287:26254–26267

    Article  PubMed  PubMed Central  Google Scholar 

  • Shockett PE, Schatz DG (1999) DNA hairpin opening mediated by the RAG1 and RAG2 proteins. Mol Cell Biol 19:4159–4166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Slade D (2018) Maneuvers on PCNA rings during DNA replication and repair. Genes (Basel) 9:416

    Article  PubMed  Google Scholar 

  • Soubeyrand S, Pope L, De Chasseval R, Gosselin D, Dong F, de Villartay J-P, Haché RJG (2006) Artemis phosphorylated by DNA-dependent protein kinase associates preferentially with discrete regions of chromatin. J Mol Biol 358:1200–1211

    Article  CAS  PubMed  Google Scholar 

  • Sun Y, Zhang Y, Aik WS, Yang X-C, Marzluff WF, Walz T, Dominski Z, Tong L (2020) Structure of an active human histone pre-mRNA 3′-end processing machinery. Science 367:700–703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Surova O, Zhivotovsky B (2013) Various modes of cell death induced by DNA damage. Oncogene 32:3789–3797

    Article  CAS  PubMed  Google Scholar 

  • Tiefenbach T, Junop M (2012) Pso2 (SNM1) is a DNA structure-specific endonuclease. Nucleic Acids Res 40:2131–2139

    Article  CAS  PubMed  Google Scholar 

  • Tiwari V, Wilson DM (2019) DNA damage and associated DNA repair defects in disease and premature aging. Am J Hum Genet 105:237–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tiwari V, Baptiste BA, Okur MN, Bohr VA (2021) Current and emerging roles of Cockayne syndrome group B (CSB) protein. Nucleic Acids Res 49:2418–2434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toma A, Takahashi TS, Sato Y, Yamagata A, Goto-Ito S, Nakada S, Fukuto A, Horikoshi Y, Tashiro S, Fukai S (2015) Structural basis for ubiquitin recognition by ubiquitin-binding zinc finger of FAAP20. PLoS One 10:e0120887

    Article  PubMed  PubMed Central  Google Scholar 

  • Tooke CL, Hinchliffe P, Bragginton EC, Colenso CK, Hirvonen VHA, Takebayashi Y, Spencer J (2019) β-Lactamases and β-lactamase inhibitors in the 21st century. J Mol Biol 431:3472–3500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Touzot F, Callebaut I, Soulier J, Gaillard L, Azerrad C, Durandy A, Fischer A, De Villartay JP, Revy P (2010) Function of Apollo (SNM1B) at telomere highlighted by a splice variant identified in a patient with Hoyeraal-Hreidarsson syndrome. Proc Natl Acad Sci U S A 107:10097–10102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Van Der Burg M, Verkaik NS, Den Dekker AT, Barendregt BH, Pico-Knijnenburg I, Tezcan I, Vandongen JJM, Van Gent DC (2007) Defective Artemis nuclease is characterized by coding joints with microhomology in long palindromic-nucleotide stretches. Eur J Immunol 37:3522–3528

    Article  PubMed  Google Scholar 

  • van Overbeek M, de Lange T (2006) Apollo, an Artemis-related nuclease, interacts with TRF2 and protects human telomeres in S phase. Curr Biol 16:1295–1302

    Article  PubMed  Google Scholar 

  • Volk T, Pannicke U, Reisli I, Bulashevska A, Ritter J, Björkman A, Schäffer AA, Fliegauf M, Sayar EH, Salzer U et al (2015) DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency. Hum Mol Genet 24:7361–7372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang AT, Sengerová B, Cattell E, Inagawa T, Hartley JM, Kiakos K, Burgess-Brown NA, Swift LP, Enzlin JH, Schofield CJ et al (2011) Human SNM1a and XPF-ERCC1 collaborate to initiate DNA interstrand cross-link repair. Genes Dev 25:1859–1870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ward IM, Minn K, van Deursen J, Chen J (2003) p53 binding protein 53BP1 is required for DNA damage responses and tumor suppression in mice. Mol Cell Biol 23:2556–2563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei H, Yu X (2016) Functions of PARylation in DNA damage repair pathways. Genomics Proteomics Bioinformatics 14:131–139

    Article  PubMed  PubMed Central  Google Scholar 

  • Wright WD, Shah SS, Heyer WD (2018) Homologous recombination and the repair of DNA double-strand breaks. J Biol Chem 293:10524–10535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu P, van Overbeek M, Rooney S, de Lange T (2010) Apollo contributes to G overhang maintenance and protects leading-end telomeres. Mol Cell 39:606–617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu P, Takai H, De Lange T (2012) Telomeric 3′ overhangs derive from resection by Exo1 and Apollo and fill-in by POT1b-associated CST. Cell 150:39–52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan Y, Akhter S, Zhang X, Legerski R (2010) The multifunctional SNM1 gene family: not just nucleases. Future Oncol 6:1015–1029

    Article  CAS  PubMed  Google Scholar 

  • Yang W (2011) Nucleases: diversity of structure, function and mechanism. Q Rev Biophys 44:1–93

    Article  PubMed  Google Scholar 

  • Yang K, Moldovan GL, D’Andrea AD (2010) RAD18-dependent recruitment of SNM1A to DNA repair complexes by a ubiquitin-binding zinc finger. J Biol Chem 285:19085–19091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Z, Liu C, Wu H, Xie Y, Gao H, Zhang X (2019) CSB affected on the sensitivity of lung cancer cells to platinum-based drugs through the global decrease of let-7 and miR-29. BMC Cancer 19:948–960

    Article  PubMed  PubMed Central  Google Scholar 

  • Yosaatmadja Y, Baddock HT, Newman JA, Bielinski M, Gavard AE, Mukhopadhyay SMM, Dannerfjord AA, Schofield CJ, McHugh PJ, Gileadi O (2021) Structural and mechanistic insights into the Artemis endonuclease and strategies for its inhibition. Nucleic Acids Res 49:9310–9326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261201800001I. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

Author information

Authors and Affiliations

  1. Discovery Biology, Curia Inc., New York, USA

    Hsuan-Yi Wu, Yuanzhang Zheng, Adrian R. Laciak, Nian N. Huang, Mary Koszelak-Rosenblum, Grant Carr & Guangyu Zhu

  2. Next CBC Support Program, Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA

    Andrew J. Flint

Authors
  1. Hsuan-Yi Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuanzhang Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adrian R. Laciak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nian N. Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mary Koszelak-Rosenblum
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrew J. Flint
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Grant Carr
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Guangyu Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guangyu Zhu .

Editor information

Editors and Affiliations

  1. Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA

    M. Zouhair Atassi

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Wu, HY. et al. (2022). Structure and Function of SNM1 Family Nucleases. In: Atassi, M.Z. (eds) Protein Reviews. Advances in Experimental Medicine and Biology(), vol 1414. Springer, Cham. https://doi.org/10.1007/5584_2022_724

Download citation

Publish with us

Policies and ethics

Search

Navigation