Skip to main content
SpringerLink
Log in

A Multifunctional Protein PolDIP2 in DNA Translesion Synthesis

  • Chapter
  • First Online:
Mechanisms of Genome Protection and Repair

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1241))

Abstract

Polymerase δ-interacting protein 2 (PolDIP2) is involved in the multiple protein-protein interactions and plays roles in many cellular processes including regulation of the nuclear redox environment, organization of the mitotic spindle and chromosome segregation, pre-mRNA processing, mitochondrial morphology and functions, cell migration and cellular adhesion. PolDIP2 is also a binding partner of high-fidelity DNA polymerase delta, PCNA and a number of translesion and repair DNA polymerases. The growing evidence suggests that PolDIP2 is a general regulatory protein in DNA damage response. However PolDIP2 functions in DNA translesion synthesis and repair are not fully understood. In this review, we address the functional interaction of PolDIP2 with human DNA polymerases and discuss the possible functions in DNA damage response.

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 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
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

References

  • Alemasova EE, Lavrik OI (2019) Poly(ADP-ribosyl)ation by PARP1: reaction mechanism and regulatory proteins. Nucleic Acids Res 47(8):3811–3827

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Arakaki N, Nishihama T, Kohda A, Owaki H, Kuramoto Y, Abe R, Kita T, Suenaga M, Himeda T, Kuwajima M, Shibata H, Higuti T (2006) Regulation of mitochondrial morphology and cell survival by Mitogenin I and mitochondrial single-stranded DNA binding protein. Biochim Biophys Acta 1760(9):1364–1372

    Article  PubMed  CAS  Google Scholar 

  • Baranovskiy AG, Lada AG, Siebler HM, Zhang Y, Pavlov YI, Tahirov TH (2012) DNA polymerase δ and ζ switch by sharing accessory subunits of DNA polymerase δ. J Biol Chem 287(21):17281–17287

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bellamacina CR (1996) The nicotinamide dinucleotide binding motif: a comparison of nucleotide binding proteins. FASEB J 10(11):1257–1269

    Article  PubMed  CAS  Google Scholar 

  • Belousova EA, Lavrik OI (2015) DNA polymerases β and λ and their roles in cell. DNA Repair (Amst) 29:112–126

    Article  CAS  Google Scholar 

  • Bianchi J, Rudd SG, Jozwiakowski SK, Bailey LJ, Soura V, Taylor E, Stevanovic I, Green AJ, Stracker TH, Lindsay HD, Doherty AJ (2013) PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication. Mol Cell 52(4):566–573

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Boehm EM, Gildenberg MS, Washington MT (2016) The many roles of PCNA in eukaryotic DNA replication. Enzyme 39:231–254

    Article  CAS  Google Scholar 

  • Boldinova EO, Wanrooij PH, Shilkin ES, Wanrooij S, Makarova AV (2017) DNA damage tolerance by eukaryotic DNA polymerase and primase PrimPol. Int J Mol Sci 18(7):E1584

    Article  PubMed  CAS  Google Scholar 

  • Bomar MG, Pai MT, Tzeng SR, Li SS, Zhou P (2007) Structure of the ubiquitin-binding zinc finger domain of human DNA Y-polymerase eta. EMBO Rep 8(3):247–251

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brown DI, Lassegue B, Lee M, Zafari R, Long JS, Saavedra HI, Griendling KK (2014) Poldip2 knockout results in perinatal lethality, reduced cellular growth and increased autophagy of mouse embryonic fibroblasts. PLoS One 9:e96657

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Burgers PM, Kunkel TA (2017) Eukaryotic DNA replication fork. Annu Rev Biochem 86:417–438

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cheng X, Kanki T, Fukuoh A, Ohgaki K, Takeya R, Aoki Y, Hamasaki N, Kang D (2005) PDIP38 associates with proteins constituting the mitochondrial DNA nucleoid. J Biochem 138(6):673–678

    Article  PubMed  CAS  Google Scholar 

  • Choe KN, Moldovan GL (2017) Forging ahead through darkness: PCNA, still the principal conductor at the replication fork. Mol Cell 65(3):380–392

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cicero DO, Contessa GM, Pertinhez TA, Gallo M, Katsuyama AM, Paci M, Farah CS, Spisni A (2007) Solution structure of ApaG from Xanthomonas axonopodis pv. citri reveals a fibronectin-3 fold. Proteins 67(2):490–500

    Article  PubMed  CAS  Google Scholar 

  • d’Alençon E, Taghbalout A, Bristow C, Kern R, Aflalo R, Kohiyama M (2003) Isolation of a new hemimethylated DNA binding protein which regulates dnaA gene expression. J Bacteriol 185(9):2967–2971

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Datla SR, McGrail DJ, Vukelic S, Huff LP, Lyle AN, Pounkova L, Lee M, Seidel-Rogol B, Khalil MK, Hilenski LL, Terada LS, Dawson MR, Lassegue B, Griendling KK (2014) Poldip2 controls vascular smooth muscle cell migration by regulating focal adhesion turnover and force polarization. Am J Physiol Heart Circ Physiol 307:H945–H957

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dieckman LM, Freudenthal BD, Washington MT (2012) PCNA structure and function: insights from structures of PCNA complexes and post-translationally modified PCNA. Subcell Biochem 62:281–299

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dym O, Eisenberg D (2001) Sequence-structure analysis of FAD-containing proteins. Protein Sci 10(9):1712–1728

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ewa B, Danuta MŠ (2017) Polycyclic aromatic hydrocarbons and PAH-related DNA adducts. J Appl Genet 58(3):321–330

    Article  PubMed  CAS  Google Scholar 

  • Garbacz MA, Lujan SA, Burkholder AB, Cox PB, Wu Q, Zhou ZX, Haber JE, Kunkel TA (2018) Evidence that DNA polymerase δ contributes to initiating leading strand DNA replication in Saccharomyces cerevisiae. Nat Commun 9(1):858

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • García-Gómez S, Reyes A, Martínez-Jiménez MI, Chocrón ES, Mourón S, Terrados G, Powell C, Salido E, Méndez J, Holt IJ, Blanco L (2013) PrimPol, an archaic primase/polymerase operating in human cells. Mol Cell 52(4):541–553

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gibson MM, Bagga DA, Miller CG, Maguire ME (1991) Magnesium transport in Salmonella typhimurium: the influence of new mutations conferring Co2+ resistance on the CorA Mg2+ transport system. Mol Microbiol 5(11):2753–2762

    Article  PubMed  CAS  Google Scholar 

  • Guilliam TA, Bailey LJ, Brissett NC, Doherty AJ (2016) PolDIP2 interacts with human PrimPol and enhances its DNA polymerase activities. Nucleic Acids Res 44(7):3317–3329

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Guo C, Tang TS, Bienko M, Parker JL, Bielen AB, Sonoda E, Takeda S, Ulrich HD, Dikic I, Friedberg EC (2006) Ubiquitin-binding motifs in REV1 protein are required for its role in the tolerance of DNA damage. Mol Cell Biol 26(23):8892–8900

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Guo C, Tang TS, Bienko M, Dikic I, Friedberg EC (2008) Requirements for the interaction of mouse Polkappa with ubiquitin and its biological significance. J Biol Chem 283(8):4658–4664

    Article  PubMed  CAS  Google Scholar 

  • Haracska L, Prakash S, Prakash L (2003) Yeast DNA polymerase zeta is an efficient extender of primer ends opposite from 7,8-dihydro-8-oxoguanine and O6-methylguanine. Mol Cell Biol 23:1453–1459

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hernandes MS, Lassègue B, Griendling KK (2017) Polymerase δ-interacting protein 2: a multifunctional protein. Cardiovasc Pharmacol 69(6):335–342

    Article  CAS  Google Scholar 

  • Ho MS, Tsai PI, Chien CT (2006) F-box proteins: the key to protein degradation. J Biomed Sci 13(2):181–191

    Article  PubMed  CAS  Google Scholar 

  • Ignatov AV, Bondarenko KA, Makarova AV (2017) Non-bulky lesions in human DNA: the ways of formation, repair, and replication. Acta Nat 9(3):12–26

    Article  CAS  Google Scholar 

  • Johnson RE, Washington MT, Haracska L, Prakash S, Prakash L (2000) Eukaryotic polymerases iota and zeta act sequentially to bypass DNA lesions. Nature 406:1015–1019

    Article  PubMed  CAS  Google Scholar 

  • Kannouche PL, Wing J, Lehmann AR (2044) Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage. Mol Cell 14(4):491–500

    Article  Google Scholar 

  • Keen BA, Jozwiakowski SK, Bailey LJ, Bianchi J, Doherty AJ (2014) Molecular dissection of the domain architecture and catalytic activities of human PrimPol. Nucleic Acids Res 42(9):5830–5845

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Klaile E, Müller MM, Kannicht C, Otto W, Singer BB, Reutter W, Obrink B, Lucka L (2007) The cell adhesion receptor carcinoembryonic antigen-related cell adhesion molecule 1 regulates nucleocytoplasmic trafficking of DNA polymerase delta-interacting protein 38. J Biol Chem 282(36):26629–26640

    Article  PubMed  CAS  Google Scholar 

  • Klaile E, Kukalev A, Obrink B, Müller MM (2008) PDIP38 is a novel mitotic spindle-associated protein that affects spindle organization and chromosome segregation. Cell Cycle 7(20):3180–3186

    Article  PubMed  CAS  Google Scholar 

  • Krzysiak TC, Chen BB, Lear T, Mallampalli RK, Gronenborn AM (2016) Crystal structure and interaction studies of the human FBxo3 ApaG domain. FEBS J 283(11):2091–2101

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee YS, Gregory MT, Yang W (2014) Human Pol ζ purified with accessory subunits is active in translesion DNA synthesis and complements Pol η in cisplatin bypass. Proc Natl Acad Sci U S A 111(8):2954–2959

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee MYWT, Wang X, Zhang S, Zhang Z, Lee EYC (2017) Regulation and modulation of human DNA polymerase δ activity and function. Genes (Basel) 8(7):pii: E190

    Article  CAS  Google Scholar 

  • Liao G, Huang J, Fixman ED, Hayward SD (2005) The Epstein-Barr virus replication protein BBLF2/3 provides an origin-tethering function through interaction with the zinc finger DNA binding protein ZBRK1 and the KAP-1 corepressor. J Virol 79(1):245–256

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu L, Rodriguez-Belmonte EM, Mazloum N, Xie B, Lee MYWT (2003) Identification of a novel protein, PDIP38, that interacts with the p50 subunit of DNA polymerase δ and proliferating cell nuclear antigen. J Biol Chem 278(12):10041–10047

    Article  PubMed  CAS  Google Scholar 

  • Lyle AN, Deshpande NN, Taniyama Y, Seidel-Rogol B, Pounkova L, Du P, Papaharalambus C, Lassegue B, Griendling KK (2009) Poldip2, a novel regulator of Nox4 and cytoskeletal integrity in vascular smooth muscle cells. Circ Res 105:249–259

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Maga G, Crespan E, Markkanen E, Imhof R, Furrer A, Villani G, Hübscher U, Van Loon B (2013) DNA polymerase δ-interacting protein 2 is a processivity factor for DNA polymerase λ during 8-oxo-7,8-dihydroguanine bypass. Proc Natl Acad Sci U S A 110(47):18850–18855

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Makarova AV, Burgers PM (2015) Eukaryotic DNA polymerase ζ. DNA Repair 29:47–55

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Makarova AV, Stodola JL, Burgers PM (2012) A four-subunit DNA polymerase ζ complex containing Pol δ accessory subunits is essential for PCNA-mediated mutagenesis. Nucleic Acids Res 40(22):11618–11626

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Makarova AV, Boldinova EO, Belousova EA, Lavrik OI (2018) In vitro lesion bypass by human PrimPol. DNA Repair (Amst) 70:18–24

    Article  CAS  Google Scholar 

  • Masutani C, Kusumoto R, Yamada A, Dohmae N, Yokoi M, Yuasa M, Araki M, Iwai S, Takio K, Hanaoka F (1999) The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta. Nature 399(6737):700–704

    Article  PubMed  CAS  Google Scholar 

  • Masutani C, Kusumoto R, Iwai S, Hanaoka F (2000) Mechanisms of accurate translesion synthesis by human DNA polymerase eta. EMBO J 19(12):3100–3109

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • McCulloch SD, Kokoska RJ, Masutani C, Iwai S, Hanaoka F, Kunkel TA (2004) Preferential cis-syn thymine dimer bypass by DNA polymerase eta occurs with biased fidelity. Nature 428(6978):97–100

    Article  PubMed  CAS  Google Scholar 

  • Mentegari E, Kissova M, Bavagnoli L, Maga G, Crespan E (2016) DNA polymerases λ and β: the double-edged swords of DNA repair. Genes (Basel) 7(9):E57

    Article  CAS  Google Scholar 

  • Mentegari E, Crespan E, Bavagnoli L, Kissova M, Bertoletti F, Sabbioneda S, Imhof R, Sturla SJ, Nilforoushan A, Hübscher U, Van Loon B, Maga G (2017) Ribonucleotide incorporation by human DNA polymerase η impacts translesion synthesis and RNase H2 activity. Nucleic Acids Res 45(5):2600–2614

    PubMed  CAS  Google Scholar 

  • Mourón S, Rodriguez-Acebes S, Martínez-Jiménez MI, García-Gómez S, Chocrón S, Blanco L, Méndez J (2013) Repriming of DNA synthesis at stalled replication forks by human PrimPol. Struct Mol Biol 20(12):1383–1389

    Article  CAS  Google Scholar 

  • Mullenders LHF (2018) Solar UV damage to cellular DNA: from mechanisms to biological effects. Photochem Photobiol Sci 17(12):1842–1852

    Article  PubMed  CAS  Google Scholar 

  • Nakajima H, Kubo T, Ihara H, Hikida T, Danjo T, Nakatsuji M, Shahani N, Itakura M, Ono Y, Azuma YT, Inui T, Kamiya A, Sawa A, Takeuchi T (2015) Nuclear-translocated glyceraldehyde-3-phosphate dehydrogenase promotes poly(ADP-ribose) polymerase-1 activation during oxidative/nitrosative stress in stroke. J Biol Chem 290(23):14493–14503

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rossmann MG, Moras D, Olsen KW (1974) Chemical and biological evolution of nucleotide-binding protein. Nature 250(463):194–199

    Article  PubMed  CAS  Google Scholar 

  • Rushing BR, Selim MI (2019) Aflatoxin B1: a review on metabolism, toxicity, occurrence in food, occupational exposure, and detoxification methods. Food Chem Toxicol 124:81–100

    Article  PubMed  CAS  Google Scholar 

  • Schiavone D, Jozwiakowski SK, Romanello M, Guilbaud G, Guilliam TA, Bailey LJ, Sale JE, Doherty AJ (2016) PrimPol is required for replicative tolerance of G quadruplexes in vertebrate cells. Mol Cell 61(1):161–169

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sharma S, Helchowski CM, Canman CE (2013) The roles of DNA polymerase ζ and the Y family DNA polymerases in promoting or preventing genome instability. Mutat Res 743–744:97–110

    Article  PubMed  CAS  Google Scholar 

  • Steinberg SF (2018) Post-translational modifications at the ATP-positioning G-loop that regulate protein kinase activity. Pharmacol Res 135:181–187

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stojkovič G, Makarova AV, Wanrooij PH, Forslund J, Burgers PM, Wanrooij S (2016) Oxidative DNA damage stalls the human mitochondrial replisome. Sci Rep 6:28942

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sutliff RL, Hilenski LL, Amanso AM, Parastatidis I, Dikalova AE, Hansen L, Datla SR, Long JS, El-Ali AM, Joseph G, Gleason RL Jr, Taylor WR, Hart CM, Griendling KK, Lassègue B (2013) Polymerase delta interacting protein 2 sustains vascular structure and function. Arterioscler Thromb Vasc Biol 33(9):2154–2161

    Article  PubMed  CAS  Google Scholar 

  • Sykora P, Kanno S, Akbari M, Kulikowicz T, Baptiste BA, Leandro GS, Lu H, Tian J, May A, Becker KA, Croteau DL, Wilson DM 3rd, Sobol RW, Yasui A, Bohr VA (2017) DNA polymerase beta participates in mitochondrial DNA repair. Mol Cell Biol 201737(16):e00237–e00217

    Google Scholar 

  • Tissier A, Janel-Bintzb R, Coulona S, Klaile E, Kannouched P, Fuchsa RP, Cordonnierb AM (2010) Crosstalk between replicative and translesional DNA polymerases: PDIP38 interacts directly with Pol η. DNA Repair 9:922–928

    Article  PubMed  CAS  Google Scholar 

  • Torregrosa-Muñumer R, Forslund JME, Goffart S, Pfeiffer A, Stojkovič G, Carvalho G, Al-Furoukh N, Blanco L, Wanrooij S, Pohjoismäki JLO (2017) PrimPol is required for replication reinitiation after mtDNA damage. Proc Natl Acad Sci U S A 114(43):11398–11403

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • van Loon B, Hübscher U (2009) An 8-oxo-guanine repair pathway coordinated by MUTYH glycosylase and DNA polymerase lambda. Proc Natl Acad Sci U S A 106(43):18201–18206

    Article  PubMed  PubMed Central  Google Scholar 

  • Wong A, Zhang S, Mordue D, Wu JM, Zhang Z, Darzynkiewicz Z, Lee EY, Lee MYWT (2013) PDIP38 is translocated to the spliceosomes/nuclear speckles in response to UV-induced DNA damage and is required for UV-induced alternative splicing of MDM2. Cell Cycle 12(19):3184–3193

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xie B, Li H, Wang Q, Xie S, Rahmeh A, Dai W, Lee MYWT (2005) Further characterization of human DNA polymerase δ interacting protein 38. J Biol Chem 280(23):22375–22384

    Article  PubMed  CAS  Google Scholar 

  • Yang W (2014) An overview of Y-Family DNA polymerases and a case study of human DNA polymerase η. Biochemistry 53:2793–2803

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yudkina AY, Shilkin ES, Endutkin AV, Makarova AV, Zharkov DO (2019) Reading and misreading 8-oxoguanine, a paradigmatic ambiguous nucleobase. Crystals 9(5):269

    Article  CAS  Google Scholar 

  • Zhou Y, Meng X, Zhang S, Lee EY, Lee MY (2012) Characterization of human DNA polymerase delta and its subassemblies reconstituted by expression in the MultiBac system. PLoS One 7:e39156

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgments

The present work was supported by the Russian Science Foundation (grant 18-14-00354) to AVM. We thank Prof. S. Wanrooij (Umea University, Sweden) for helpful discussion and suggestions.

Author information

Authors and Affiliations

  1. RAS Institute of Molecular Genetics, Moscow, Russia

    Diana I. Gagarinskaya & Alena V. Makarova

Authors
  1. Diana I. Gagarinskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alena V. Makarova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alena V. Makarova .

Editor information

Editors and Affiliations

  1. Novosibirsk State University, Novosibirsk, Russia

    Dmitry O. Zharkov

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Gagarinskaya, D.I., Makarova, A.V. (2020). A Multifunctional Protein PolDIP2 in DNA Translesion Synthesis. In: Zharkov, D. (eds) Mechanisms of Genome Protection and Repair. Advances in Experimental Medicine and Biology, vol 1241. Springer, Cham. https://doi.org/10.1007/978-3-030-41283-8_3

Download citation

Publish with us

Policies and ethics

Search

Navigation