Skip to main content
SpringerLink
Log in

DNA Damage Signaling Downstream of ATM

  • Chapter
  • First Online:
Molecular Determinants of Radiation Response

Part of the book series: Current Cancer Research ((CUCR))

Abstract

ATM is the apical signaling molecule that triggers diverse cellular responses to double-strand DNA breaks. Directly and indirectly, ATM initiates a two-tiered cascade of protein kinase activation, composed of upstream phosphatidylinositol 3-kinase-like kinases, mediator proteins, and checkpoint kinases. Together, these proteins signal a broad network of downstream effectors that modulate virtually every aspect of cell growth and death. This review will focus on the signaling molecules required for the diverse ATM-dependent responses to DNA damage, with an emphasis on the extensively characterized pathways that suppress proliferation and promote DNA repair.

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 169.99
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

References

  • Abraham RT (2001) Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev 15:2177–96

    Article  PubMed  CAS  Google Scholar 

  • Adams KE, Medhurst AL, Dart DA et al (2006) Recruitment of ATR to sites of ionising radiation-induced DNA damage requires ATM and components of the MRN protein complex. Oncogene 25:3894–904

    Article  PubMed  CAS  Google Scholar 

  • Aglipay JA, Martin SA, Tawara H et al (2006) ATM activation by ionizing radiation requires BRCA1-associated BAAT1. J Biol Chem 281:9710–8

    Article  PubMed  CAS  Google Scholar 

  • Ahn J, Urist M, Prives C (2004) The Chk2 protein kinase. DNA Repair (Amst) 3:1039–47

    Article  CAS  Google Scholar 

  • Alderton GK, Galbiati L, Griffith E et al (2006) Regulation of mitotic entry by microcephalin and its overlap with ATR signalling. Nat Cell Biol 8:725–33

    Article  PubMed  CAS  Google Scholar 

  • Appella E, Anderson CW (2001) Post-translational modifications and activation of p53 by genotoxic stresses. Eur J Biochem 268:2764–72.

    Article  PubMed  CAS  Google Scholar 

  • Bakkenist CJ, Kastan MB (2004) Initiating cellular stress responses. Cell 118:9–17

    Article  PubMed  CAS  Google Scholar 

  • Bartek J, Lukas J (2003) Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 3:421–9

    Article  PubMed  CAS  Google Scholar 

  • Bartek J, Falck J, Lukas J (2001) CHK2 kinase – a busy messenger. Nat Rev Mol Cell Biol 2:877–86.

    Article  PubMed  CAS  Google Scholar 

  • Bell DW, Varley JM, Szydlo TE et al (1999) Heterozygous germ line hCHK2 mutations in Li–Fraumeni syndrome. Science 286:2528–31

    Article  PubMed  CAS  Google Scholar 

  • Boutros R, Dozier C, Ducommun B (2006) The when and wheres of CDC25 phosphatases. Curr Opin Cell Biol 18:185–91

    Article  PubMed  CAS  Google Scholar 

  • Brown EJ, Baltimore D (2003) Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance. Genes Dev 17:615–28

    Article  PubMed  CAS  Google Scholar 

  • Canman CE, Wolff AC, Chen CY et al (1994) The p53-dependent G1 cell cycle checkpoint pathway and ataxia- telangiectasia. Cancer Res 54:5054–8

    PubMed  CAS  Google Scholar 

  • Canman CE, Lim DS, Cimprich KA et al (1998) Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science 281:1677–9

    Article  PubMed  CAS  Google Scholar 

  • Casper AM, Nghiem P, Arlt MF et al (2002) ATR regulates fragile site stability. Cell 111:779–89

    Article  PubMed  CAS  Google Scholar 

  • Chao C, Herr D, Chun J et al (2006) Ser18 and 23 phosphorylation is required for p53-dependent apoptosis and tumor suppression. EMBO J 25:2615–22

    PubMed  CAS  Google Scholar 

  • Chehab NH, Malikzay A, Appel M et al (2000) Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53. Genes Dev 14:278–88

    PubMed  CAS  Google Scholar 

  • Chini CC, Chen J (2004) Claspin, a regulator of Chk1 in DNA replication stress pathway. DNA Repair (Amst) 3:1033–7

    Article  CAS  Google Scholar 

  • Chini CC, Chen J (2006) Repeated phosphopeptide motifs in human Claspin are phosphorylated by Chk1 and mediate Claspin function. J Biol Chem 281:33276–82

    Article  PubMed  CAS  Google Scholar 

  • Cimprich KA, Cortez D (2008) ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol 9:616–27

    Article  PubMed  CAS  Google Scholar 

  • Cortez D, Wang Y, Qin J et al (1999) Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks. Science 286:1162–6

    Article  PubMed  CAS  Google Scholar 

  • Cortez D, Guntuku S, Qin J et al (2001) ATR and ATRIP: Partners in Checkpoint Signaling. Science 294:1713–6

    Article  PubMed  CAS  Google Scholar 

  • Cuadrado M, Martinez-Pastor B, Murga M et al (2006) ATM regulates ATR chromatin loading in response to DNA double-strand breaks. J Exp Med 203:297–303

    Article  PubMed  CAS  Google Scholar 

  • Deng CX (2006) BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution. Nucleic Acids Res 34:1416–26

    Article  PubMed  CAS  Google Scholar 

  • DiTullio RA Jr, Mochan TA, Venere M et al (2002) 53BP1 functions in an ATM-dependent checkpoint pathway that is constitutively activated in human cancer. Nat Cell Biol 4:998–1002

    Article  PubMed  CAS  Google Scholar 

  • Dodson GE, Tibbetts RS (2006) DNA replication stress-induced phosphorylation of cyclic AMP response element-binding protein mediated by ATM. J Biol Chem 281:1692–7

    Article  PubMed  CAS  Google Scholar 

  • Fanning E, Klimovich V, Nager AR (2006) A dynamic model for replication protein A (RPA) function in DNA processing pathways. Nucleic Acids Res 34:4126–37

    Article  PubMed  CAS  Google Scholar 

  • Gatei M, Sloper K, Sorensen C et al (2003) Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation. J Biol Chem 278:14806–11

    Article  PubMed  CAS  Google Scholar 

  • Goldberg M, Stucki M, Falck J et al (2003) MDC1 is required for the intra-S-phase DNA damage checkpoint. Nature 421:952–6

    Article  PubMed  CAS  Google Scholar 

  • Gurtan AM, D’Andrea AD (2006) Dedicated to the core: understanding the Fanconi anemia complex. DNA Repair (Amst) 5:1119–25

    Article  CAS  Google Scholar 

  • Hirao A, Kong YY, Matsuoka S et al (2000) DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science 287:1824–7

    Article  PubMed  CAS  Google Scholar 

  • Horn HF, Vousden KH (2007) Coping with stress: multiple ways to activate p53. Oncogene 26:1306–16

    Article  PubMed  CAS  Google Scholar 

  • Hurley PJ, Bunz F (2007) ATM and ATR: Components of an integrated circuit. Cell Cycle 6:414–7

    Article  PubMed  CAS  Google Scholar 

  • Hurley PJ, Wilsker D, Bunz F (2007) Human cancer cells require ATR for cell cycle progression following exposure to ionizing radiation. Oncogene 26:2535–42

    Article  PubMed  CAS  Google Scholar 

  • Huyen Y, Zgheib O, Ditullio RA Jr et al (2004) Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 432:406–11

    Article  PubMed  CAS  Google Scholar 

  • Iwabuchi K, Bartel PL, Li B et al (1994) Two cellular proteins that bind to wild-type but not mutant p53. Proc Natl Acad Sci USA 91:6098-102

    Article  PubMed  CAS  Google Scholar 

  • Jack MT, Woo RA, Hirao A et al (2002) Chk2 is dispensable for p53-mediated G1 arrest but is required for a latent p53-mediated apoptotic response. Proc Natl Acad Sci USA 3:3

    Google Scholar 

  • Jallepalli PV, Lengauer C, Vogelstein B et al (2003) The Chk2 tumor suppressor is not required for p53 responses in human cancer cells. J Biol Chem 278:20475–9

    Article  PubMed  CAS  Google Scholar 

  • Jazayeri A, Falck J, Lukas C et al (2006) ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat Cell Biol 8:37–45

    Article  PubMed  CAS  Google Scholar 

  • Jowsey P, Morrice NA, Hastie CJ et al (2007) Characterisation of the sites of DNA damage-induced 53BP1 phosphorylation catalysed by ATM and ATR. DNA Repair (Amst) 6:1536–44

    Article  CAS  Google Scholar 

  • Karlsson-Rosenthal C, Millar JB (2006) Cdc25: mechanisms of checkpoint inhibition and ­recovery. Trends Cell Biol 16:285–92

    Article  PubMed  CAS  Google Scholar 

  • Kastan MB, Lim DS (2000) The many substrates and functions of ATM. Nat Rev Mol Cell Biol 1:179–86

    Article  PubMed  CAS  Google Scholar 

  • Kruse JP, Gu W (2008) SnapShot: p53 posttranslational modifications. Cell 133:930–30.e1

    Article  PubMed  CAS  Google Scholar 

  • Kruse JP, Gu W (2009) Modes of p53 regulation. Cell 137:609–22

    Article  PubMed  CAS  Google Scholar 

  • Kubbutat MH, Jones SN, Vousden KH (1997) Regulation of p53 stability by Mdm2. Nature 387:299–303

    Article  PubMed  CAS  Google Scholar 

  • Kumagai A, Dunphy WG (2000) Claspin, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts. Mol Cell 6:839–49

    Article  PubMed  CAS  Google Scholar 

  • Kumagai A, Dunphy WG (2003) Repeated phosphopeptide motifs in Claspin mediate the regulated binding of Chk1. Nat Cell Biol 5:161–5

    Article  PubMed  CAS  Google Scholar 

  • Kumagai A, Dunphy WG (2006) How cells activate ATR. Cell Cycle 5:1265–8

    Article  PubMed  CAS  Google Scholar 

  • Lavin MF, Birrell G, Chen P et al (2005) ATM signaling and genomic stability in response to DNA damage. Mutat Res 569:123–32

    Article  PubMed  CAS  Google Scholar 

  • Lee JS, Collins KM, Brown AL et al (2000) hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response. Nature 404:201–4

    Article  PubMed  CAS  Google Scholar 

  • Lee J, Kumagai A, Dunphy WG (2007) The Rad9-Hus1-Rad1 checkpoint clamp regulates interaction of TopBP1 with ATR. J Biol Chem 282:28036–44

    Article  PubMed  CAS  Google Scholar 

  • Lin SY, Rai R, Li K et al (2005) BRIT1/MCPH1 is a DNA damage responsive protein that regulates the Brca1-Chk1 pathway, implicating checkpoint dysfunction in microcephaly. Proc Natl Acad Sci USA 102:15105–9

    Article  PubMed  CAS  Google Scholar 

  • Liu Q, Guntuku S, Cui XS et al (2000) Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev 14:1448–59

    Article  PubMed  CAS  Google Scholar 

  • Liu S, Bekker-Jensen S, Mailand N et al (2006) Claspin operates downstream of TopBP1 to direct ATR signaling towards Chk1 activation. Mol Cell Biol 26:6056–64

    Article  PubMed  CAS  Google Scholar 

  • Lukas C, Melander F, Stucki M et al (2004) Mdc1 couples DNA double-strand break recognition by Nbs1 with its H2AX-dependent chromatin retention. EMBO J 23:2674–83

    Article  PubMed  CAS  Google Scholar 

  • MacPherson D, Kim J, Kim T et al (2004) Defective apoptosis and B-cell lymphomas in mice with p53 point mutation at Ser 23. EMBO J 23:3689–99

    Article  PubMed  CAS  Google Scholar 

  • Manke IA, Nguyen A, Lim D et al (2005) MAPKAP kinase-2 is a cell cycle checkpoint kinase that regulates the G2/M transition and S phase progression in response to UV irradiation. Mol Cell 17:37–48

    Article  PubMed  CAS  Google Scholar 

  • Matsuoka S, Ballif BA, Smogorzewska A et al (2007) ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316:1160–6

    Article  PubMed  CAS  Google Scholar 

  • McGowan CH (2002) Checking in on Cds1 (Chk2): A checkpoint kinase and tumor suppressor. Bioessays 24:502–11

    Article  PubMed  CAS  Google Scholar 

  • McGowan CH and Russell P (2004) The DNA damage response: sensing and signaling. Curr Opin Cell Biol 16:629-633

    Article  PubMed  CAS  Google Scholar 

  • Meijers-Heijboer H, van den Ouweland A, Klijn J et al (2002) Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet 31:55–9

    Article  PubMed  CAS  Google Scholar 

  • Mochan TA, Venere M, DiTullio RA Jr et al (2003) 53BP1 and NFBD1/MDC1-Nbs1 function in parallel interacting pathways activating ataxia-telangiectasia mutated (ATM) in response to DNA damage. Cancer Res 63:8586–91

    PubMed  CAS  Google Scholar 

  • Mohammad DH, Yaffe MB (2009) 14-3-3 proteins, FHA domains and BRCT domains in the DNA damage response. DNA Repair (Amst) 8:1009–17

    Article  CAS  Google Scholar 

  • Mordes DA, Glick GG, Zhao R et al (2008) TopBP1 activates ATR through ATRIP and a PIKK regulatory domain. Genes Dev 22:1478–89

    Article  PubMed  CAS  Google Scholar 

  • Myers JS, Cortez D (2006) Rapid activation of ATR by ionizing radiation requires ATM and Mre11. J Biol Chem 281:9346–50

    Article  PubMed  CAS  Google Scholar 

  • Niida H, Katsuno Y, Banerjee B et al (2007) Specific role of Chk1 phosphorylations in cell survival and checkpoint activation. Mol Cell Biol 27:2572–81

    Article  PubMed  CAS  Google Scholar 

  • O’Driscoll M, Gennery AR, Seidel J et al (2004) An overview of three new disorders associated with genetic instability: LIG4 syndrome, RS-SCID and ATR–Seckel syndrome. DNA Repair (Amst) 3:1227–235

    Article  CAS  Google Scholar 

  • Okada S, Ouchi T (2003) Cell cycle differences in DNA damage-induced BRCA1 phosphorylation affect its subcellular localization. J Biol Chem 278:2015–20

    Article  PubMed  CAS  Google Scholar 

  • Oliver AW, Knapp S, Pearl LH (2007) Activation segment exchange: a common mechanism of kinase autophosphorylation? Trends Biochem Sci 32:351–6

    Article  PubMed  CAS  Google Scholar 

  • Osborn AJ, Elledge SJ, Zou L (2002) Checking on the fork: the DNA-replication stress-response pathway. Trends Cell Biol 12:509–16

    Article  PubMed  CAS  Google Scholar 

  • Ouchi T (2006) BRCA1 phosphorylation: biological consequences. Cancer Biol Ther 5:470–5

    Article  PubMed  CAS  Google Scholar 

  • Parrilla-Castellar ER, Arlander SJ, Karnitz L (2004) Dial 9-1-1 for DNA damage: the Rad9-Hus1-Rad1 (9-1-1) clamp complex. DNA Repair (Amst) 3:1009–14

    Article  CAS  Google Scholar 

  • Peng G, Yim EK, Dai H et al (2009) BRIT1/MCPH1 links chromatin remodelling to DNA damage response. Nat Cell Biol 11:865–72

    Article  PubMed  CAS  Google Scholar 

  • Puc J, Parsons R (2005) PTEN loss inhibits CHK1 to cause double stranded-DNA breaks in cells. Cell Cycle 4:927–9

    Article  PubMed  CAS  Google Scholar 

  • Puc J, Keniry M, Li HS et al (2005) Lack of PTEN sequesters CHK1 and initiates genetic instability. Cancer Cell 7:193–204

    Article  PubMed  CAS  Google Scholar 

  • Reinhardt HC, Yaffe MB (2009) Kinases that control the cell cycle in response to DNA damage: Chk1, Chk2, and MK2. Curr Opin Cell Biol 21:245–5

    Article  PubMed  CAS  Google Scholar 

  • Roux PP, Blenis J (2004) ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev 68:320–44

    Article  PubMed  CAS  Google Scholar 

  • Saito S, Yamaguchi H, Higashimoto Y et al (2003) Phosphorylation site interdependence of human p53 post-translational modifications in response to stress. J Biol Chem 278:37536–44

    Article  PubMed  CAS  Google Scholar 

  • Shieh SY, Ahn J, Tamai K et al (2000) The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev 14:289–300

    PubMed  CAS  Google Scholar 

  • Shiloh Y (2006) The ATM-mediated DNA-damage response: taking shape. Trends Biochem Sci 31:402–10

    Article  PubMed  CAS  Google Scholar 

  • Sluss HK, Armata H, Gallant J et al (2004) Phosphorylation of serine 18 regulates distinct p53 functions in mice. Mol Cell Biol 24:976–84

    Article  PubMed  CAS  Google Scholar 

  • Smits VA (2006) Spreading the signal: dissociation of Chk1 from chromatin. Cell Cycle 5:1039–43

    Article  PubMed  CAS  Google Scholar 

  • Smits VA, Reaper PM, Jackson SP (2006) Rapid PIKK-dependent release of Chk1 from chromatin promotes the DNA-damage checkpoint response. Curr Biol 16:150–9

    Article  PubMed  CAS  Google Scholar 

  • Sodha N, Williams R, Mangion J et al (2000) Screening hCHK2 for mutations. Science 289:359.

    Article  PubMed  CAS  Google Scholar 

  • Sodha N, Houlston RS, Bullock S et al (2002) Increasing evidence that germline mutations in CHEK2 do not cause Li–Fraumeni syndrome. Hum Mutat 20:460–2

    Article  PubMed  CAS  Google Scholar 

  • Stewart GS, Wang B, Bignell CR et al (2003) MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature 421:961–6

    Article  PubMed  CAS  Google Scholar 

  • Stiff T, Walker SA, Cerosaletti K et al (2006) ATR-dependent phosphorylation and activation of ATM in response to UV treatment or replication fork stalling. EMBO J 25:5775–82

    Article  PubMed  CAS  Google Scholar 

  • Stokes MP, Comb MJ (2008) A wide-ranging cellular response to UV damage of DNA. Cell Cycle 7:2097–9

    Article  PubMed  CAS  Google Scholar 

  • Stokes MP, Rush J, Macneill J et al (2007) Profiling of UV-induced ATM/ATR signaling pathways. Proc Natl Acad Sci USA 104:19855–60

    Article  PubMed  CAS  Google Scholar 

  • Stracker TH, Usui T, Petrini JH (2009) Taking the time to make important decisions: the checkpoint effector kinases Chk1 and Chk2 and the DNA damage response. DNA Repair (Amst) 8:1047–54

    Article  CAS  Google Scholar 

  • Stucki M, Jackson SP (2004) MDC1/NFBD1: a key regulator of the DNA damage response in higher eukaryotes. DNA Repair (Amst) 3:953–7

    Article  CAS  Google Scholar 

  • Tibbetts RS, Brumbaugh KM, Williams JM et al (1999) A role for ATR in the DNA damage-induced phosphorylation of p53. Genes Dev 13:152–7

    Article  PubMed  CAS  Google Scholar 

  • Vogelstein B, Lane D, Levine AJ (2000) Surfing the p53 network. Nature 408:307–10

    Article  PubMed  CAS  Google Scholar 

  • Wang B, Matsuoka S, Carpenter PB et al (2002) 53BP1, a mediator of the DNA damage checkpoint. Science 298:1435–8

    Article  PubMed  CAS  Google Scholar 

  • Wang X, Zou L, Lu T et al (2006) Rad17 phosphorylation is required for claspin recruitment and Chk1 activation in response to replication stress. Mol Cell 23:331–41

    Article  PubMed  CAS  Google Scholar 

  • Wang X, Kennedy RD, Ray K et al (2007) Chk1-mediated phosphorylation of FANCE is required for the Fanconi anemia/BRCA pathway. Mol Cell Biol 27:3098–108

    Article  PubMed  CAS  Google Scholar 

  • Ward IM, Minn K, van Deursen J et al (2003) p53 Binding protein 53BP1 is required for DNA damage responses and tumor suppression in mice. Mol Cell Biol 23:2556–63

    Article  PubMed  CAS  Google Scholar 

  • Ward IM, Minn K, Chen J (2004) UV-induced ataxia-telangiectasia-mutated and Rad3-related (ATR) activation requires replication stress. J Biol Chem 279:9677–80

    Article  PubMed  CAS  Google Scholar 

  • Ward IM, Difilippantonio S, Minn K et al (2005) 53BP1 cooperates with p53 and functions as a haploinsufficient tumor suppressor in mice. Mol Cell Biol 25:10079–86

    Article  PubMed  CAS  Google Scholar 

  • Ward I, Kim JE, Minn K et al (2006) The tandem BRCT domain of 53BP1 is not required for its repair function. J Biol Chem 281:38472–7

    Article  PubMed  CAS  Google Scholar 

  • Weischer M, Bojesen SE, Ellervik C et al (2008) CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls. J Clin Oncol 26:542–8

    Article  PubMed  Google Scholar 

  • Wilsker D, Petermann E, Helleday T et al (2008) Essential function of Chk1 can be uncoupled from DNA damage checkpoint and replication control. Proc Natl Acad Sci USA 105:20752–7

    Article  PubMed  CAS  Google Scholar 

  • Wilson KA, Stern DF (2008) NFBD1/MDC1, 53BP1 and BRCA1 have both redundant and unique roles in the ATM pathway. Cell Cycle 7:3584–94

    Article  PubMed  CAS  Google Scholar 

  • Wu Z, Earle J, Saito S et al (2002) Mutation of mouse p53 Ser23 and the response to DNA damage. Mol Cell Biol 22:2441–9

    Article  PubMed  CAS  Google Scholar 

  • Xiao Z, Xue J, Sowin TJ et al (2006) Differential roles of checkpoint kinase 1, checkpoint kinase 2, and mitogen-activated protein kinase-activated protein kinase 2 in mediating DNA damage-induced cell cycle arrest: implications for cancer therapy. Mol Cancer Ther 5:1935–43

    Article  PubMed  CAS  Google Scholar 

  • Xu B, Kim S, Kastan MB (2001) Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing irradiation. Mol Cell Biol 21:3445–50

    Article  PubMed  CAS  Google Scholar 

  • Xu X, Lee J, Stern DF (2004) Microcephalin is a DNA damage response protein involved in regulation of CHK1 and BRCA1. J Biol Chem 279:34091–4

    Article  PubMed  CAS  Google Scholar 

  • Xu C, Wu L, Cui G et al (2008) Structure of a second BRCT domain identified in the nijmegen breakage syndrome protein Nbs1 and its function in an MDC1-dependent localization of Nbs1 to DNA damage sites. J Mol Biol 381:361–72

    Article  PubMed  CAS  Google Scholar 

  • Yu X, Chini CC, He M et al (2003) The BRCT domain is a phospho-protein binding domain. Science 302:639–42

    Article  PubMed  CAS  Google Scholar 

  • Zegerman P, Diffley JF (2009) DNA replication as a target of the DNA damage checkpoint. DNA Repair (Amst) 8:1077–88

    Article  CAS  Google Scholar 

  • Zhang J, Willers H, Feng Z et al (2004) Chk2 phosphorylation of BRCA1 regulates DNA double-strand break repair. Mol Cell Biol 24:708–18

    Article  PubMed  CAS  Google Scholar 

  • Zhao H, Piwnica-Worms H (2001) ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Mol Cell Biol 21:4129–39

    Article  PubMed  CAS  Google Scholar 

  • Zou L, Elledge SJ (2003) Sensing DNA damage through ATRIP recognition of RPA–ssDNA complexes. Science 300:1542–8

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, David H. Koch Cancer Research Building (CRB2), Room 453, 1550 Orleans Street, CRB II, Room 462, Baltimore, MD, 21231, USA

    Fred Bunz (Associate Professor)

Authors
  1. Fred Bunz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fred Bunz .

Editor information

Editors and Affiliations

  1. Dept. Radiation Oncology, Johns Hopkins University, N. Wolfe Street 600, Baltimore, 21287, Maryland, USA

    Theodore L. DeWeese

  2. Dept. Radiation Oncology, Johns Hopkins University, Orleans Street 1550, Baltimore, 21231, Maryland, USA

    Marikki Laiho

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Bunz, F. (2011). DNA Damage Signaling Downstream of ATM. In: DeWeese, T., Laiho, M. (eds) Molecular Determinants of Radiation Response. Current Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-8044-1_2

Download citation

Publish with us

Policies and ethics

Search

Navigation