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How homologous recombination maintains telomere integrity

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Abstract

Telomeres protect the ends of linear chromosomes against loss of genetic information and inappropriate processing as damaged DNA and are therefore crucial to the maintenance of chromosome integrity. In addition to providing a pathway for genome-wide DNA repair, homologous recombination (HR) plays a key role in telomere replication and capping. Consistent with this, the genomic instability characteristic of HR-deficient cells and tumours is driven in part by telomere dysfunction. Here, we discuss the mechanisms by which HR modulates the response to intrinsic cellular challenges that arise during telomere replication, as well as its impact on the assembly of telomere protective structures. How normal and tumour cells differ in their ability to maintain telomeres is deeply relevant to the search for treatments that would selectively eliminate cells whose capacity for HR-mediated repair has been compromised.

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References

  • Abreu E, Aritonovska E, Reichenbach P, Cristofari G, Culp B, Terns RM, Lingner J, Terns MP (2010) TIN2-tethered TPP1 recruits human telomerase to telomeres in vivo. Mol Cell Biol 30:2971–2982

    PubMed Central  CAS  PubMed  Google Scholar 

  • Amiard S, Doudeau M, Pinte S, Poulet A, Lenain C, Faivre-Moskalenko C, Angelov D, Hug N, Vindigni A, Bouvet P et al (2007) A topological mechanism for TRF2-enhanced strand invasion. Nat Struct Mol Biol 14:147–154

    CAS  PubMed  Google Scholar 

  • Azzalin CM, Reichenbach P, Khoriauli L, Giulotto E, Lingner J (2007) Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science 318:798–801

    CAS  PubMed  Google Scholar 

  • Badie S, Escandell JM, Bouwman P, Carlos AR, Thanasoula M, Gallardo MM, Suram A, Jaco I, Benitez J, Herbig U et al (2010) BRCA2 acts as RAD51 loader to facilitate telomere replication and capping. Nat Struct Mol Biol 17:1461–1469

    PubMed Central  CAS  PubMed  Google Scholar 

  • Baird DM, Jeffreys AJ, Royle NJ (1995) Mechanisms underlying telomere repeat turnover, revealed by hypervariable variant repeat distribution patterns in the human Xp/Yp telomere. EMBO J 14:5433–5443

    PubMed Central  CAS  PubMed  Google Scholar 

  • Baumann P, Cech TR (2001) Pot1, the putative telomere end-binding protein in fission yeast and humans. Science 292:1171–1175

    CAS  PubMed  Google Scholar 

  • Bermejo R, Lai MS, Foiani M (2012) Preventing replication stress to maintain genome stability: resolving conflicts between replication and transcription. Mol Cell 45:710–718

    CAS  PubMed  Google Scholar 

  • Bhatia V, Barroso SI, García-Rubio ML, Tumini E, Herrera-Moyano E, Aguilera A (2014) BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export factor PCID2. Nature 511:362–365

    CAS  PubMed  Google Scholar 

  • Bilaud T, Brun C, Ancelin K, Koering CE, Laroche T, Gilson E (1997) Telomeric localization of TRF2, a novel human telobox protein. Nat Genet 17:236–239

    CAS  PubMed  Google Scholar 

  • Blackburn EH (1984) Telomeres: do the ends justify the means? Cell 37:7–8

    CAS  PubMed  Google Scholar 

  • Blasco MA (2007) The epigenetic regulation of mammalian telomeres. Nat Rev Genet 8:299–309

    CAS  PubMed  Google Scholar 

  • Bouwman P, Aly A, Escandell JM, Pieterse M, Bartkova J, van der Gulden H, Hiddingh S, Thanasoula M, Kulkarni A, Yang Q et al (2010) 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nat Struct Mol Biol 17:688–695

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bunting SF, Callén E, Wong N, Chen HT, Polato F, Gunn A, Bothmer A, Feldhahn N, Fernandez-Capetillo O, Cao L et al (2010) 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 141:243–254

    PubMed Central  CAS  PubMed  Google Scholar 

  • Carlos AR, Escandell JM, Kotsantis P, Suwaki N, Bouwman P, Badie S, Folio C, Benitez J, Gomez-Lopez G, Pisano D et al (2013) ARF triggers senescence in Brca2-deficient cells by altering the spectrum of p53 transcriptional targets. Nat Commun 4:2697

    PubMed  Google Scholar 

  • Celli GB, de Lange T (2005) DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion. Nat Cell Biol 7:712–718

    CAS  PubMed  Google Scholar 

  • Chapman JR, Barral P, Vannier JB, Borel V, Steger M, Tomas-Loba A, Sartori AA, Adams IR, Batista FD, Boulton SJ (2013) RIF1 is essential for 53BP1-dependent nonhomologous end joining and suppression of DNA double-strand break resection. Mol Cell 49:858–871

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chong L, van Steensel B, Broccoli D, Erdjument-Bromage H, Hanish J, Tempst P, de Lange T (1995) A human telomeric protein. Science 270:1663–1667

    CAS  PubMed  Google Scholar 

  • Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40:179–204

    PubMed Central  CAS  PubMed  Google Scholar 

  • Conomos D, Pickett HA, Reddel RR (2013) Alternative lengthening of telomeres: remodeling the telomere architecture. Front Oncol 3:1–7

    Google Scholar 

  • Conrad MN, Wright JH, Wolf AJ, Zakian VA (1990) RAP1 protein interacts with yeast telomeres in vivo: overproduction alters telomere structure and decreases chromosome stability. Cell 63:739–750

    CAS  PubMed  Google Scholar 

  • Crabbe L, Verdun RE, Haggblom CI, Karlseder J (2004) Defective telomere lagging strand synthesis in cells lacking WRN helicase activity. Science 306:1951–1953

    CAS  PubMed  Google Scholar 

  • Denchi EL, de Lange T (2007) Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature 448:1068–1071

    CAS  PubMed  Google Scholar 

  • Deng Z, Dheekollu J, Broccoli D, Dutta A, Lieberman PM (2007) The origin recognition complex localizes to telomere repeats and prevents telomere-circle formation. Curr Biol 17:1989–1995

    CAS  PubMed  Google Scholar 

  • Deng Z, Norseen J, Wiedmer A, Riethman H, Lieberman PM (2009) TERRA RNA binding to TRF2 facilitates heterochromatin formation and ORC recruitment at telomeres. Mol Cell 35:403–413

    PubMed Central  CAS  PubMed  Google Scholar 

  • Di Virgilio M, Callen E, Yamane A, Zhang W, Jankovic M, Gitlin AD, Feldhahn N, Resch W, Oliveira TY, Chait BT et al (2013) Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching. Science 339:711–715

    PubMed  Google Scholar 

  • Ding H, Schertzer M, Wu X, Gertsenstein M, Selig S, Kammori M, Pourvali R, Poon S, Vulto I, Chavez E et al (2004) Cell 117:873–886

    CAS  PubMed  Google Scholar 

  • Doksani Y, Wu JY, de Lange T, Zhuang X (2013) Super-resolution fluorescence imaging of telomeres reveals TRF2-dependent T-loop formation. Cell 155:345–356

    PubMed Central  CAS  PubMed  Google Scholar 

  • Drosopoulos WC, Kosiyatrakul ST, Yan Z, Calderano SG, Schildkraut CL (2012) Human telomeres replicate using chromosome-specific, rather than universal, replication programs. J Cell Biol 197:253–266

    PubMed Central  CAS  PubMed  Google Scholar 

  • Dunham MA, Neumann AA, Fasching CL, Reddel RR (2000) Telomere maintenance by recombination in human cells. Nat Genet 26:447–450

    CAS  PubMed  Google Scholar 

  • Dunn B, Szauter P, Pardue ML, Szostak JW (1984) Transfer of yeast telomeres to linear plasmids by recombination. Cell 39:191–201

    CAS  PubMed  Google Scholar 

  • Escribano-Díaz C, Orthwein A, Fradet-Turcotte A, Xing M, Young JT, Tkáč J, Cook MA, Rosebrock AP, Munro M, Canny MD et al (2013) A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice. Mol Cell 49:872–883

    PubMed  Google Scholar 

  • Fang G, Cech TR (1993) The beta subunit of Oxytricha telomere-binding protein promotes G-quartet formation by telomeric DNA. Cell 74:875–885

    CAS  PubMed  Google Scholar 

  • Flynn RL, Centore RC, O’Sullivan RJ, Rai R, Tse A (2011) TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA. Nature 471:532–536

    PubMed Central  CAS  PubMed  Google Scholar 

  • Fry M, Loeb LA (1999) Human Werner syndrome DNA helicase unwinds tetrahelical structures of the fragile X syndrome repeat sequence d(CGG)n. J Biol Chem 274:12797–12802

    CAS  PubMed  Google Scholar 

  • Gilson E, Géli V (2007) How telomeres are replicated. Nat Rev Mol Cell Biol 8:825–838

    CAS  PubMed  Google Scholar 

  • Greider CW (1996) Telomere length regulation. Annu Rev Biochem 65:337–365

    CAS  PubMed  Google Scholar 

  • Greider CW, Blackburn EH (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43:405–413

    CAS  PubMed  Google Scholar 

  • Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T (1999) Mammalian telomeres end in a large duplex loop. Cell 97:503–514

    CAS  PubMed  Google Scholar 

  • Hashimoto Y, Chaudhuri AI, Lopez M, Costanzo V (2010) Rad51 protects nascent DNA from Mre11-dependent degradation and promotes continuous DNA synthesis. Nat Struct Mol Biol 17:1305–1311

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–636

    CAS  PubMed  Google Scholar 

  • Holliday R (1964) A mechanism for gene conversion in fungi. Genet Res 5:282–304

    Google Scholar 

  • Houghtaling BR, Cuttonaro L, Chang W, Smith S (2004) A dynamic molecular link between the telomere length regulator TRF1 and the chromosome end protector TRF2. Curr Biol 14:1621–1631

    CAS  PubMed  Google Scholar 

  • Huber MD, Duquette ML, Shiels JC, Maizels N (2006) A conserved G4 DNA binding domain in RecQ family helicases. J Mol Biol 358:1071–1080

    CAS  PubMed  Google Scholar 

  • Jaco I, Munoz P, Goytisolo F, Wesoly J, Bailey S, Taccioli G, Blasco MA (2003) Role of mammalian Rad54 in telomere length maintenance. Mol Cell Biol 23:5572–5580

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jones RE, Oh S, Grimstead JW, Zimbric J, Roger L, Heppel NH, Ashelford KE, Liddiard K, Hendrickson EA, Baird DM (2014) Escape from telomere-driven crisis Is DNA ligase III dependent. Cell Rep 8:1063–1076

    CAS  PubMed  Google Scholar 

  • Kahn T, Savitsky M, Georgiev P (2000) Attachment of HeT-A sequences to chromosomal termini in Drosophila melanogaster may occur by different mechanisms. Mol Cell Biol 20:7634–7642

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kappei D, Butter F, Benda C, Scheibe M, Draskovic I, Stevense M, Novo CL, Basquin C, Araki M, Araki K et al (2013) HOT1 is a mammalian direct telomere repeat-binding protein contributing to telomerase recruitment. EMBO J 32:1681–1701

    PubMed Central  CAS  PubMed  Google Scholar 

  • Le S, Moore JK, Haber JE, Greider CW (1999) RAD50 and RAD51 define two pathways that collaborate to maintain telomeres in the absence of telomerase. Genetics 152:143–152

    PubMed Central  CAS  PubMed  Google Scholar 

  • Li BM, Oestreich S, de Lange T (2000) Identification of human RAP1: implications for telomere evolution. Cell 101:471–483

    CAS  PubMed  Google Scholar 

  • Lin TT, Norris K, Heppel NH, Pratt G, Allan JM, Allsup DJ, Bailey J, Cawkwell L, Hills R, Grimstead JW et al (2014) Telomere dysfunction accurately predicts clinical outcome in chronic lymphocytic leukaemia, even in patients with early stage disease. Br J Haematol. doi:10.1111/bjh.13023

    Google Scholar 

  • Lipps HJ, Rhodes D (2009) G-quadruplex structures: in vivo evidence and function. Trends Cell Biol 19:414–422

    CAS  PubMed  Google Scholar 

  • Liu Y, West SC (2004) Happy Hollidays: 40th anniversary of the Holliday junction. Nat Rev Mol Cell Biol 5:937–946

    CAS  PubMed  Google Scholar 

  • Liu D, Safari A, O’Connor MS, Chan DW, Laegeler A, Qin J, Songyang Z (2004a) PTOP interacts with POT1 and regulates its localization to telomeres. Nat Cell Biol 6:673–680

    CAS  PubMed  Google Scholar 

  • Liu Y, Masson J-Y, Shah R, O’Regan P, West SC (2004b) RAD51C is required for Holliday junction processing in mammalian cells. Science 303:243–246

    CAS  PubMed  Google Scholar 

  • Loayza D, de Lange T (2003) POT1 as a terminal transducer of TRF1 telomere length control. Nature 423:1013–1018

    CAS  PubMed  Google Scholar 

  • Lundblad V, Blackburn EH (1993) An alternative pathway for yeast telomere maintenance rescues est1- senescence. Cell 73:347–360

    CAS  PubMed  Google Scholar 

  • Martínez P, Blasco MA (2011) Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins. Nat Rev Cancer 11:161–176

    PubMed  Google Scholar 

  • Martinez P, Thanasoula M, Munoz P, Liao C, Tejera A, McNees C, Flores JM, Fernandez-Capetillo O, Tarsounas M, Blasco MA (2009) Increased telomere fragility and fusions resulting from TRF1 deficiency lead to degenerative pathologies and increased cancer in mice. Genes Dev 23:2060–2075

    PubMed Central  CAS  PubMed  Google Scholar 

  • Martinez P, Thanasoula M, Carlos AR, Gómez-López G, Tejera A, Schoeftner S, Dominguez O, Pisano D, Tarsounas M, Blasco MA (2010) Mammalian Rap1 controls telomere function and gene expression through binding to telomeric and extratelomeric sites. Nat Cell Biol 12:768–780

    PubMed Central  CAS  PubMed  Google Scholar 

  • Maser RS, DePinho RA (2002) Connecting chromosomes, crisis, and cancer. Science 297:565–569

    CAS  PubMed  Google Scholar 

  • McClintock B (1941) The stability of broken ends of chromosomes in Zea mays. Genetics 26:234–282

    PubMed Central  CAS  PubMed  Google Scholar 

  • Mimitou EP, Symington LS (2011) DNA end resection-unraveling the tail. DNA Repair (Amst) 10:344–348

    CAS  Google Scholar 

  • Miyake Y, Nakamura M, Nabetani A, Shimamura S, Tamura M, Yonehara S, Saito M, Ishikawa F (2009) RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-stranded DNA and protects telomeres independently of the Pot1 pathway. Mol Cell 36:193–206

    CAS  PubMed  Google Scholar 

  • Neumann AA, Watson CM, Noble JR, Pickett HA, Tam PP, Reddel RR (2013) Alternative lengthening of telomeres in normal mammalian somatic cells. Genes Dev 27:18–23

    PubMed Central  CAS  PubMed  Google Scholar 

  • Nimonkar AV, Genschel J, Kinoshita E, Polaczek P, Campbell JL, Wyman C, Modrich P, Kowalczykowski SC (2011) BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. Genes Dev 25:350–362

    PubMed Central  CAS  PubMed  Google Scholar 

  • Opresko PL, von Kobbe C, Laine JP, Harrigan J, Hickson ID, Bohr VA (2002) Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases. J Biol Chem 277:41110–41119

    CAS  PubMed  Google Scholar 

  • Opresko PL, Cheng WH, von Kobbe C, Harrigan JA, Bohr VA (2003) Werner syndrome and the function of the Werner protein; what they can teach us about the molecular aging process. Carcinogenesis 24:791–802

    CAS  PubMed  Google Scholar 

  • Palm W, de Lange T (2008) How shelterin protects mammalian telomeres. Annu Rev Genet 42:16.11–16.34

    Google Scholar 

  • Pardue ML, DeBaryshe PG (2011) Retrotransposons that maintain chromosome ends. Proc Natl Acad Sci U S A 108:20317–20324

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pellegrini L, Yu DS, Lo T, Anand S, Lee MY, Blundell TL, Venkitaraman AR (2002) Insights into DNA recombination from the structure of a RAD51-BRCA2 complex. Nature 420:287–293

    CAS  PubMed  Google Scholar 

  • Pfeiffer V, Crittin J, Grolimund L, Lingner J (2013) The THO complex component Thp2 counteracts telomeric R-loops and telomere shortening. EMBO J 32:2861–2871

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pluta AF, Zakian VA (1989) Recombination occurs during telomere formation in yeast. Nature 337:429–433

    CAS  PubMed  Google Scholar 

  • Poulet A, Buisson R, Faivre-Moskalenko C, Koelblen M, Amiard S, Montel F, Cuesta-Lopez S, Bornet O, Guerlesquin F, Godet T et al (2009) TRF2 promotes, remodels and protects telomeric Holliday junctions. EMBO J 28:641–651

    PubMed Central  CAS  PubMed  Google Scholar 

  • Redon S, Reichenbach P, Lingner J (2010) The non-coding RNA TERRA is a natural ligand and direct inhibitor of human telomerase. Nucleic Acids Res 38:5797–5806

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ribeyre C, Lopes J, Boulé JB, Piazza A, Guédin A, Zakian VA, Mergny JL, Nicolas A (2009) The yeast Pif1 helicase prevents genomic instability caused by G-quadruplex-forming CEB1 sequences in vivo. PLoS Genet 5

  • Roger L, Jones RE, Heppel NH, Williams GT, Sampson JR, Baird DM (2013) Extensive telomere erosion in the initiation of colorectal adenomas and its association with chromosomal instability. J Natl Cancer Inst 105:1202–1211

    CAS  PubMed  Google Scholar 

  • Roth CW, Kobeski F, Walter MF, Biessmann H (1997) Chromosome end elongation by recombination in the mosquito Anopheles gambiae. Mol Cell Biol 17:5176–5183

    PubMed Central  CAS  PubMed  Google Scholar 

  • Savitsky M, Kravchuk O, Melnikova L, Georgiev P (2002) Heterochromatin protein 1 is involved in control of telomere elongation in Drosophila melanogaster. Mol Cell Biol 22:3204–3218

    PubMed Central  CAS  PubMed  Google Scholar 

  • Schlacher K, Christ N, Siaud N, Egashira A, Wu H, Jasin M (2011) Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11. Cell 145:529–542

    PubMed Central  CAS  PubMed  Google Scholar 

  • Schoeftner S, Blasco MA (2008) Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nat Cell Biol 10:228–236

    CAS  PubMed  Google Scholar 

  • Schoeftner S, Blasco MA (2009) A ‘higher order’ of telomere regulation: telomere heterochromatin and telomeric RNAs. EMBO J 28:2323–2336

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sfeir A, Kosiyatrakul ST, Hockemeyer D, MacRae SL, Karlseder J, Schildkraut CL, de Lange T (2009) Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell 138:90–103

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sfeir A, Kabir S, van Overbeek M, Celli GB, de Lange T (2010) Loss of Rap1 induces telomere recombination in the absence of NHEJ or a DNA damage signal. Science 327:1657–1661

    PubMed Central  CAS  PubMed  Google Scholar 

  • Smith JS, Chen Q, Yatsunyk LA, Nicoludis JM, Garcia MS, Kranaster R, Balasubramanian S, Monchaud D, Teulade-Fichou MP, Abramowitz L et al (2011) Rudimentary G-quadruplex-based telomere capping in Saccharomyces cerevisiae. Nat Struct Mol Biol 18:478–485

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sun H, Karow JK, Hickson ID, Maizels N (1998) The Bloom’s syndrome helicase unwinds G4 DNA. J Biol Chem 273:27587–27592

    CAS  PubMed  Google Scholar 

  • Suwaki N, Klare K, Tarsounas M (2011) RAD51 paralogs: roles in DNA damage signalling, recombinational repair and tumorigenesis. Semin Cell Dev Biol 22:898–905

  • Szostak JW, Blackburn EH (1982) Cloning yeast telomeres on linear plasmid vectors. Cell 29:245–255

    CAS  PubMed  Google Scholar 

  • Szostak JW, Orr-Weaver TL, Rothstein RJ, Stahl FW (1983) The double-strand-break repair model for recombination. Cell 33:25–35

    CAS  PubMed  Google Scholar 

  • Tahara H, Shin-Ya K, Seimiya H, Yamada H, Tsuruo T, Ide T (2006) G-Quadruplex stabilization by telomestatin induces TRF2 protein dissociation from telomeres and anaphase bridge formation accompanied by loss of the 3′ telomeric overhang in cancer cells. Oncogene 25:1955–1966

    CAS  PubMed  Google Scholar 

  • Takai KK, Kibe T, Donigian JR, Frescas D, de Lange T (2011) Telomere protection by TPP1/POT1 requires tethering to TIN2. Mol Cell 44:647–659

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tarsounas M, Tijsterman M (2013) Genomes and G-quadruplexes: for better or for worse. J Mol Biol 425:4782–4789

    CAS  PubMed  Google Scholar 

  • Tarsounas M, West SC (2005) Recombination at mammalian telomeres: an alternative mechanism for telomere protection and elongation. Cell Cycle 4:672–674

    CAS  PubMed  Google Scholar 

  • Tarsounas M, Muñoz P, Claas A, Smiraldo PG, Pittman DL, Blasco MA, West SC (2004) Telomere maintenance requires the RAD51D recombination/repair protein. Cell 117:337–347

    CAS  PubMed  Google Scholar 

  • Teixeira MT, Arneric M, Sperisen P, Lingner J (2004) Telomere length homeostasis is achieved via a switch between telomerase-extendible and -nonextendible states. Cell 117:323–335

    CAS  PubMed  Google Scholar 

  • Tejera A, Stagno d’Alcontres M, Thanasoula M, Martinez P, Liao C, Tarsounas M, Blasco MA (2010) TPP1 is required for TERT recruitment, telomere elongation during nuclear reprogramming, and normal skin development in mice. Dev Cell 18:775–789

    PubMed Central  CAS  PubMed  Google Scholar 

  • Teo H, Ghosh S, Luesch H, Ghosh A, Wong ET, Malik N, Orth A, de Jesus P, Perry AS, Oliver JD et al (2010) Telomere-independent Rap1 is an IKK adaptor and regulates NF-kappaB-dependent gene expression. Nat Cell Biol 12:758–767

    CAS  PubMed  Google Scholar 

  • van Steensel B, Smogorzewska A, de Lange T (1998) TRF2 protects human telomeres from end-to-end fusions. Cell 92:401–413

    PubMed  Google Scholar 

  • Vannier JB, Pavicic-Kaltenbrunner V, Petalcorin MI, Ding H, Boulton SJ (2012) RTEL1 dismantles T loops and counteracts telomeric G4-DNA to maintain telomere integrity. Cell 149:795–806

    CAS  PubMed  Google Scholar 

  • Vannier J-B, Sandhu S, Petalcorin MI, Wu X, Nabi Z, Ding H, Boulton SJ (2013) RTEL1 is a replisome-associated helicase that promotes telomere and genome-wide replication. Science 342:239–242

    CAS  PubMed  Google Scholar 

  • Verdun RE, Karlseder J (2006) The DNA damage machinery and homologous recombination pathway act consecutively to protect human telomeres. Cell 127:709–720

    CAS  PubMed  Google Scholar 

  • Wan M, Qin J, Songyang Z, Liu D (2009) OB fold-containing protein 1 (OBFC1), a human homolog of yeast Stn1, associates with TPP1 and is implicated in telomere length regulation. J Biol Chem 284:26725–26731

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wang S-S, Zakian VA (1990) Telomere-telomere recombination provides an express pathway for telomere elongation. Nature 345:456–458

    CAS  PubMed  Google Scholar 

  • Wang RC, Smogorzewska A, de Lange T (2004) Homologous recombination generates T-loop-sized deletions at human telomeres. Cell 119:355–368

    CAS  PubMed  Google Scholar 

  • Watson JD, Crick FHC (1953) Genetical implications of the structure of deoxyribonucleic acid. Nature 171:964

    CAS  PubMed  Google Scholar 

  • West SC (2009) The search for a human Holliday junction resolvase. Biochem Soc Trans 37:519–526

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wu L, Multani AS, He H, Cosme-Blanco W, Deng Y, Deng JM, Bachilo O, Pathak S, Tahara H, Bailey SM et al (2006) Pot1 deficiency initiates DNA damage checkpoint activation and aberrant homologous recombination at telomeres. Cell 126:49–62

    CAS  PubMed  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

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ye JZ, de Lange T (2004) TIN2 is a tankyrase 1 PARP modulator in the TRF1 telomere length control complex. Nat Genet 36:618–623

    CAS  PubMed  Google Scholar 

  • Ye JZ, Hockemeyer D, Krutchinsky AN, Loayza D, Hooper SM, Chait BT, de Lange T (2004) POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex. Genes Dev 18:1649–1654

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ye J, Lenain C, Bauwens S, Rizzo A, Saint-Léger A, Poulet A, Benarroch D, Magdinier F, Morere J, Amiard S et al (2010) TRF2 and apollo cooperate with topoisomerase 2alpha to protect human telomeres from replicative damage. Cell 142:230–242

    CAS  PubMed  Google Scholar 

  • Zimmermann M, Lottersberger F, Buonomo SB, Sfeir A, de Lange T (2013) 53BP1 regulates DSB repair using Rif1 to control 5′ end resection. Science 339:700–704

    PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

EMCT is funded by a Medical Research Council PhD Studentship. Work in MT laboratory is supported by Cancer Research UK, EMBO Young Investigator Award and The Royal Society.

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  1. Telomere and Genome Stability Group, The CRUK-MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK

    Eliana M. C. Tacconi & Madalena Tarsounas

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  1. Eliana M. C. Tacconi
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Correspondence to Madalena Tarsounas.

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Tacconi, E.M.C., Tarsounas, M. How homologous recombination maintains telomere integrity. Chromosoma 124, 119–130 (2015). https://doi.org/10.1007/s00412-014-0497-2

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