Collaboration and competition between DNA double‐strand break repair pathways

DNA double‐strand breaks resulting from normal cellular processes including replication and exogenous sources such as ionizing radiation pose a serious risk to genome stability, and cells have evolved different mechanisms for their efficient repair. The two major pathways involved in the repair of double‐strand breaks in eukaryotic cells are non‐homologous end joining and homologous recombination. Numerous factors affect the decision to repair a double‐strand break via these pathways, and accumulating evidence suggests these major repair pathways both cooperate and compete with each other at double‐strand break sites to facilitate efficient repair and promote genomic integrity.

[1]  J. Haber,et al.  Removal of nonhomologous DNA ends in double-strand break recombination: the role of the yeast ultraviolet repair gene RAD1. , 1992, Science.

[2]  H. Vogel,et al.  Deletion of Ku86 causes early onset of senescence in mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Junjie Chen,et al.  PALB2 is an integral component of the BRCA complex required for homologous recombination repair , 2009, Proceedings of the National Academy of Sciences.

[4]  David J. Chen,et al.  DNA-dependent protein kinase suppresses double-strand break-induced and spontaneous homologous recombination , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[5]  F. Alt,et al.  Distinct roles of chromatin-associated proteins MDC1 and 53BP1 in mammalian double-strand break repair. , 2007, Molecular cell.

[6]  M. Jasin,et al.  Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis , 2010, Nature Reviews Molecular Cell Biology.

[7]  Tom L. Blundell,et al.  Insights into DNA recombination from the structure of a RAD51–BRCA2 complex , 2002, Nature.

[8]  Wen-Hwa Lee,et al.  BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure. , 2002, Science.

[9]  Eleni P. Mimitou,et al.  Nucleases and helicases take center stage in homologous recombination. , 2009, Trends in biochemical sciences.

[10]  S. Jackson,et al.  DNA end-joining: from yeast to man. , 1998, Trends in biochemical sciences.

[11]  E. Kass,et al.  Loss of 53BP1 is a gain for BRCA1 mutant cells. , 2010, Cancer cell.

[12]  M. Lieber,et al.  The Mechanism of Human Nonhomologous DNA End Joining* , 2008, Journal of Biological Chemistry.

[13]  F. Couch,et al.  Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. , 2006, Molecular cell.

[14]  M. Lieber,et al.  Efficient Processing of DNA Ends during Yeast Nonhomologous End Joining , 1999, The Journal of Biological Chemistry.

[15]  A. Ashworth,et al.  Interaction between the Product of the Breast Cancer Susceptibility Gene BRCA2 and DSS1, a Protein Functionally Conserved from Yeast to Mammals , 1999, Molecular and Cellular Biology.

[16]  P. Dhar,et al.  Genetic Analysis of the DNA-dependent Protein Kinase Reveals an Inhibitory Role of Ku in Late S–G2 Phase DNA Double-strand Break Repair* , 2001, The Journal of Biological Chemistry.

[17]  Yunmei Ma,et al.  The Artemis:DNA-PKcs endonuclease cleaves DNA loops, flaps, and gaps. , 2005, DNA repair.

[18]  D. Weinstock,et al.  Alternative Pathways for the Repair of RAG-Induced DNA Breaks , 2006, Molecular and Cellular Biology.

[19]  Junjie Chen,et al.  PALB2 Regulates Recombinational Repair through Chromatin Association and Oligomerization* , 2009, The Journal of Biological Chemistry.

[20]  D. Adams,et al.  53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers , 2010, Nature Structural &Molecular Biology.

[21]  J. Petrini,et al.  The Mre11-Rad50-Xrs2 Protein Complex Facilitates Homologous Recombination-Based Double-Strand Break Repair inSaccharomyces cerevisiae , 1999, Molecular and Cellular Biology.

[22]  Luca Pellegrini,et al.  A region of human BRCA2 containing multiple BRC repeats promotes RAD51-mediated strand exchange , 2006, Nucleic acids research.

[23]  Maximina H. Yun,et al.  CtIP-BRCA1 modulates the choice of DNA double-strand break repair pathway throughout the cell cycle , 2009, Nature.

[24]  Jeremy M. Stark,et al.  Extensive Loss of Heterozygosity Is Suppressed during Homologous Repair of Chromosomal Breaks , 2003, Molecular and Cellular Biology.

[25]  Xiaohua Wu,et al.  Cell Cycle-dependent Complex Formation of BRCA1·CtIP·MRN Is Important for DNA Double-strand Break Repair* , 2008, Journal of Biological Chemistry.

[26]  M. Jasin,et al.  Ku80-deficient Cells Exhibit Excess Degradation of Extrachromosomal DNA* , 1996, The Journal of Biological Chemistry.

[27]  J. Haber,et al.  Saccharomyces Ku70, Mre11/Rad50, and RPA Proteins Regulate Adaptation to G2/M Arrest after DNA Damage , 1998, Cell.

[28]  Jeremy M. Stark,et al.  Genetic Steps of Mammalian Homologous Repair with Distinct Mutagenic Consequences , 2004, Molecular and Cellular Biology.

[29]  C. Bendixen,et al.  DNA strand annealing is promoted by the yeast Rad52 protein. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Fan Zhang,et al.  PALB2 Functionally Connects the Breast Cancer Susceptibility Proteins BRCA1 and BRCA2 , 2009, Molecular Cancer Research.

[31]  N. Pavletich,et al.  Mechanism of homologous recombination from the RecA–ssDNA/dsDNA structures , 2008, Nature.

[32]  J. Hoeijmakers,et al.  Mouse RAD54 Affects DNA Double-Strand Break Repair and Sister Chromatid Exchange , 2000, Molecular and Cellular Biology.

[33]  A. Tomkinson,et al.  Role of Dnl4–Lif1 in nonhomologous end-joining repair complex assembly and suppression of homologous recombination , 2007, Nature Structural &Molecular Biology.

[34]  Jeremy M. Stark,et al.  Alternative-NHEJ Is a Mechanistically Distinct Pathway of Mammalian Chromosome Break Repair , 2008, PLoS genetics.

[35]  S. Keeney,et al.  Evolutionary conservation of meiotic DSB proteins: more than just Spo11. , 2010, Genes & development.

[36]  Jeremy M. Stark,et al.  53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by Blocking Resection of DNA Breaks , 2010, Cell.

[37]  Kai Rothkamm,et al.  Pathways of DNA Double-Strand Break Repair during the Mammalian Cell Cycle , 2003, Molecular and Cellular Biology.

[38]  M. Jasin,et al.  Chromosomal translocation mechanisms at intronic alu elements in mammalian cells. , 2005, Molecular cell.

[39]  James E Haber,et al.  Heteroduplex rejection during single-strand annealing requires Sgs1 helicase and mismatch repair proteins Msh2 and Msh6 but not Pms1. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[40]  F. Alt,et al.  Mechanism and control of V(D)J recombination versus class switch recombination: similarities and differences. , 2005, Advances in immunology.

[41]  Ian D. Hickson,et al.  RecQ helicases: multifunctional genome caretakers , 2009, Nature Reviews Cancer.

[42]  Y. Yamaguchi-Iwai,et al.  Homologous recombination and non‐homologous end‐joining pathways of DNA double‐strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells , 1998, The EMBO journal.

[43]  Sang Eun Lee,et al.  Sgs1 Helicase and Two Nucleases Dna2 and Exo1 Resect DNA Double-Strand Break Ends , 2008, Cell.

[44]  Stephen P. Jackson,et al.  Human CtIP Mediates Cell Cycle Control of DNA End Resection and Double Strand Break Repair*S⃞ , 2009, Journal of Biological Chemistry.

[45]  P. Bartel,et al.  RAD51 Interacts with the Evolutionarily Conserved BRC Motifs in the Human Breast Cancer Susceptibility Gene brca2 * , 1997, The Journal of Biological Chemistry.

[46]  Yunmei Ma,et al.  A biochemically defined system for mammalian nonhomologous DNA end joining. , 2004, Molecular cell.

[47]  M. Kupiec,et al.  The CDK regulates repair of double‐strand breaks by homologous recombination during the cell cycle , 2004, The EMBO journal.

[48]  L. Symington,et al.  Breaking Up Just Got Easier to Do , 2009, Cell.

[49]  Jeremy M. Stark,et al.  Double-strand breaks and tumorigenesis. , 2001, Trends in cell biology.

[50]  A. Ashworth,et al.  Mutation in Brca2 stimulates error‐prone homology‐directed repair of DNA double‐strand breaks occurring between repeated sequences , 2001, The EMBO journal.

[51]  F. Alt,et al.  DNA double strand break repair and chromosomal translocation: Lessons from animal models , 2001, Oncogene.

[52]  M. Jasin,et al.  BRCA2 is required for homology-directed repair of chromosomal breaks. , 2001, Molecular cell.

[53]  F. Alt,et al.  Collaboration of homologous recombination and nonhomologous end-joining factors for the survival and integrity of mice and cells. , 2004, Genes & development.

[54]  M. Eijpe,et al.  Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis , 1999, Nature Genetics.

[55]  Rafael Núñez,et al.  BRCA1 promotes induction of ssDNA by ionizing radiation. , 2006, Cancer research.

[56]  N. Sternberg,et al.  Model for homologous recombination during transfer of DNA into mouse L cells: role for DNA ends in the recombination process , 1984, Molecular and cellular biology.

[57]  M. J. Neale,et al.  Endonucleolytic processing of covalent protein-linked DNA double-strand breaks , 2005, Nature.

[58]  Jeremy M. Stark,et al.  Limiting the Persistence of a Chromosome Break Diminishes Its Mutagenic Potential , 2009, PLoS genetics.

[59]  Edward H Egelman,et al.  Stabilization of RAD51 nucleoprotein filaments by the C-terminal region of BRCA2 , 2007, Nature Structural &Molecular Biology.

[60]  J. Bartek,et al.  The DNA-damage response in human biology and disease , 2009, Nature.

[61]  F. Fabre.  Induced intragenic recombination in yeast can occur during the G1 mitotic phase , 1978, Nature.

[62]  Paul Modrich,et al.  Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair , 2008, Proceedings of the National Academy of Sciences.

[63]  S. Jackson,et al.  CDK targets Sae2 to control DNA-end resection and homologous recombination , 2008, Nature.

[64]  M. Jasin,et al.  An xrcc4 defect or Wortmannin stimulates homologous recombination specifically induced by double-strand breaks in mammalian cells. , 2002, Nucleic acids research.

[65]  Y. Pommier,et al.  Collaborative Action of Brca1 and CtIP in Elimination of Covalent Modifications from Double-Strand Breaks to Facilitate Subsequent Break Repair , 2010, PLoS genetics.

[66]  Z. Hořejší,et al.  Preventing nonhomologous end joining suppresses DNA repair defects of Fanconi anemia. , 2010, Molecular cell.

[67]  C. Deng,et al.  A selective requirement for 53BP1 in the biological response to genomic instability induced by Brca1 deficiency. , 2009, Molecular cell.

[68]  M. Frank-Vaillant,et al.  Transient stability of DNA ends allows nonhomologous end joining to precede homologous recombination. , 2002, Molecular cell.

[69]  Jiri Bartek,et al.  Human CtIP promotes DNA end resection , 2007, Nature.

[70]  J. Griffith,et al.  Synapsis of DNA ends by DNA‐dependent protein kinase , 2002, The EMBO journal.

[71]  F. Alt,et al.  Rad54 and DNA Ligase IV cooperate to maintain mammalian chromatid stability. , 2004, Genes & development.

[72]  David Klenerman,et al.  The BRC repeats of human BRCA2 differentially regulate RAD51 binding on single- versus double-stranded DNA to stimulate strand exchange , 2009, Proceedings of the National Academy of Sciences.

[73]  Abby Dernburg,et al.  Homologous Chromosome Pairing in Drosophila melanogaster Proceeds through Multiple Independent Initiations , 1998, The Journal of cell biology.

[74]  A. Ashworth,et al.  DSS1 is required for RAD51 focus formation and genomic stability in mammalian cells , 2004, EMBO reports.

[75]  Ashok R. Venkitaraman,et al.  The BRC Repeats of BRCA2 Modulate the DNA-Binding Selectivity of RAD51 , 2009, Cell.

[76]  Marco Foiani,et al.  DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1 , 2004, Nature.

[77]  C. E. Schrader,et al.  Mechanism and regulation of class switch recombination. , 2008, Annual review of immunology.

[78]  Michael M. Murphy,et al.  IgH class switching and translocations use a robust non-classical end-joining pathway , 2007, Nature.

[79]  Zhao-Qi Wang,et al.  Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[80]  Weidong Wang.  Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins , 2007, Nature Reviews Genetics.

[81]  Eleni P. Mimitou,et al.  Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing , 2008, Nature.

[82]  N. Ellis,et al.  Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells. , 2001, Genes & development.

[83]  Naomi Kondo,et al.  Selective utilization of nonhomologous end-joining and homologous recombination DNA repair pathways during nervous system development. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[84]  Junjie Chen,et al.  DNA Damage-Induced Cell Cycle Checkpoint Control Requires CtIP, a Phosphorylation-Dependent Binding Partner of BRCA1 C-Terminal Domains , 2004, Molecular and Cellular Biology.

[85]  M. Jasin,et al.  Alternative end-joining is suppressed by the canonical NHEJ component Xrcc4/ligase IV during chromosomal translocation formation , 2010, Nature Structural &Molecular Biology.

[86]  K. Schwarz,et al.  The embryonic lethality in DNA ligase IV-deficient mice is rescued by deletion of Ku: implications for unifying the heterogeneous phenotypes of NHEJ mutants. , 2002, DNA repair.

[87]  Y. Taniguchi,et al.  Genetic dissection of vertebrate 53BP1: a major role in non-homologous end joining of DNA double strand breaks. , 2006, DNA repair.

[88]  J. Haber,et al.  Genetic requirements for the single-strand annealing pathway of double-strand break repair in Saccharomyces cerevisiae. , 1996, Genetics.

[89]  G E Tomlinson,et al.  BRCA2 is required for ionizing radiation-induced assembly of Rad51 complex in vivo. , 1999, Cancer research.

[90]  M. Lieber,et al.  Requirement for an Interaction of XRCC4 with DNA Ligase IV for Wild-type V(D)J Recombination and DNA Double-strand Break Repairin Vivo * , 1998, The Journal of Biological Chemistry.

[91]  M. Sivasubramaniam,et al.  Ku70 Corrupts DNA Repair in the Absence of the Fanconi Anemia Pathway , 2010, Science.

[92]  P. Sung,et al.  Mechanism of eukaryotic homologous recombination. , 2008, Annual review of biochemistry.

[93]  S. West,et al.  CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair , 2005, Nature.

[94]  B. Koller,et al.  Brca1 controls homology-directed DNA repair. , 1999, Molecular cell.