The MRN complex: Coordinating and mediating the response to broken chromosomes

EMBO Reports

Volumn 4, Issue 9, 2003, Pages 844-849

  van den Bosch, Michael ^a   Bree, Ronan T ^a   Lowndes, Noel F ^a  

^a NATIONAL UNIVERSITY OF IRELAND   (Ireland)

Author keywords

[No Author keywords available]

Indexed keywords

CELL PROTEIN; DOUBLE STRANDED DNA; ATM PROTEIN; DNA DAMAGE CHECKPOINT PROTEIN 1; MRE11 PROTEIN; MRN COMPLEX; MULTIPROTEIN COMPLEX; NIBRIN; PROTEIN; RAD50 PROTEIN; UNCLASSIFIED DRUG;

CHROMOSOME DAMAGE; DNA DAMAGE; DNA METABOLISM; DNA STRAND BREAKAGE; ESSENTIAL GENE; GENE MUTATION; GENETIC STABILITY; GENOME; HUMAN; IMMUNOPRECIPITATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DNA BINDING; PROTEIN FUNCTION; REVIEW; VERTEBRATE; CELL ACTIVATION; CHROMOSOME BREAKAGE; CORRELATION ANALYSIS; DNA BINDING; DNA REPAIR; DOUBLE STRANDED DNA BREAK; GENOMIC INSTABILITY; MOLECULAR BIOLOGY; PROTEIN LOCALIZATION;

ANIMALS; CELL CYCLE PROTEINS; CHROMOSOME ABERRATIONS; DNA DAMAGE; DNA REPAIR; DNA REPAIR ENZYMES; DNA-BINDING PROTEINS; HUMANS; NUCLEAR PROTEINS; PROTEIN-SERINE-THREONINE KINASES; TUMOR SUPPRESSOR PROTEINS;

VERTEBRATA;

EID: 0142186242     PISSN: 1469221X     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.embor.embor925     Document Type: Review

References (47)

1. Bakkenist, C.J. & Kastan, M.B. (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature, 421, 499-506.
2. Barnes, D.E. (2001) Non-homologous end joining as a mechanism of DNA repair. Curr. Biol., 11, R455-R457.
3. S/S mice. Genes Dev., 16, 2237-2251.
4. Bressan, D.A., Baxter, B.K. & Petrini, J.H. (1999) The Mre11-Rad50-Xrs2 protein complex facilitates homologous recombination-based double-strand break repair in Saccharomyces cerevisiae. Mol. Cell. Biol., 19, 7681-7687.
5. Burma, S., Chen, B.P., Murphy, M., Kurimasa, A. & Chen, D.J. (2001) ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J. Biol. Chem., 276, 42462-42467.
6. Buscemi, G. et al. (2001) Chk2 activation dependence on Nbs1 after DNA damage. Mol. Cell. Biol., 21, 5214-5222.
7. Celeste, A. et al. (2002) Genomic instability in mice lacking histone H2AX. Science, 296, 922-927.
8. D'Amours, D. & Jackson, S.P. (2002) The Mre11 complex: at the crossroads of DNA repair and checkpoint signalling. Nature Rev. Mol. Cell Biol., 3, 317-327.
9. de Jager, M., van Noort, J., van Gent, D.C., Dekker, C., Kanaar, R. & Wyman, C. (2001) Human Rad50/Mre11 is a flexible complex that can tether DNA ends. Mol. Cell, 8, 1129-1135.
10. de Jager, M., Wyman, C., van Gent, D.C. & Kanaar, R. (2002) DNA end-binding specificity of human Rad50/Mre11 is influenced by ATP. Nucleic Acids Res., 30, 4425-4431.
11. Downs, J.A., Lowndes, N.F. & Jackson, S.P. (2000) A role for Saccharomyces cerevisiae histone H2A in DNA repair. Nature, 408, 1001-1004.
12. Falck, J., Petrini, J.H., Williams, B.R., Lukas, J. & Bartek, J. (2002) The DNA damage-dependent intra-S phase checkpoint is regulated by parallel pathways. Nature Genet., 30, 290-294.
13. Fernandez-Capetillo, O. et al. (2002) DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1. Nature Cell Biol., 4, 993-997.
14. Foray, N. et al. (2003) A subset of ATM- and ATR-dependent phosphorylation events requires the BRCA1 protein. EMBO J., 22, 2860-2871.
15. Gatei, M. et al. (2000) ATM-dependent phosphorylation of nibrin in response to radiation exposure. Nature Genet., 25, 115-119.
16. Goldberg, M. et al. (2003) MDC1 is required for the intra-S-phase DNA damage checkpoint. Nature, 421, 952-956.
17. Hirano, T. (2002) The ABCs of SMC proteins: two-armed ATPases for chromosome condensation, cohesion, and repair. Genes Dev., 16, 399-414.
18. Hopfner, K.P., Karcher, A., Craig, L., Woo, T.T., Carney, J.P. & Tainer, J.A. (2001) Structural biochemistry and interaction architecture of the DNA double-strand break repair Mre11 nuclease and Rad50-ATPase. Cell, 105, 473-485.
19. Hopfner, K.P. et al. (2002) The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair. Nature, 418, 562-566.
20. Kang, J., Bronson, R.T. & Xu, Y. (2002) Targeted disruption of NBS1 reveals its roles in mouse development and DNA repair. EMBO J., 21, 1447-1455.
21. Kim, S.T., Xu, B. & Kastan, M.B. (2002) Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damage. Genes Dev., 16, 560-570.
22. Lim, D.S. et al. (2000) ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway. Nature, 404, 613-617.
23. Lobachev, K.S., Gordenin, D.A. & Resnick, M.A. (2002) The Mre11 complex is required for repair of hairpin-capped double-strand breaks and prevention of chromosome rearrangements. Cell, 108, 183-193.
24. Lou, Z., Chini, C.C., Minter-Dykhouse, K. & Chen, J. (2003) Mediator of DNA damage checkpoint protein 1 regulates BRCA1 localization and phosphorylation in DNA damage checkpoint control. J. Biol. Chem., 278, 13599-13602.
25. Luo, G. et al. (1999) Disruption of mRad50 causes embryonic stem cell lethality, abnormal embryonic development, and sensitivity to ionizing radiation. Proc. Natl Acad. Sci. USA, 96, 7376-7381.
26. Maser, R.S., Monsen, K.J., Nelms, B.E. & Petrini, J.H. (1997) hMRE11 and hRad50 nuclear foci are induced during the normal cellular response to DNA double-strand breaks. Mol. Cell. Biol., 17, 6087-6096.
27. Mirzoeva, O.K. & Petrini, J.H. (2001) DNA damage-dependent nuclear dynamics of the Mre11 complex. Mol. Cell. Biol., 21, 281-288.
28. Mirzoeva, O.K. & Petrini, J.H. (2003) DNA replication-dependent nuclear dynamics of the mre11 complex. Mol. Cancer Res., 1, 207-218.
29. Moreau, S., Ferguson, J.R. & Symington, L.S. (1999) The nuclease activity of Mre11 is required for meiosis but not for mating type switching, end joining, or telomere maintenance. Mol. Cell. Biol., 19, 556-566.
30. Nelms, B.E., Maser, R.S., MacKay, J.F, Lagally, M.G. & Petrini, J.H. (1998) In situ visualization of DNA double-strand break repair in human fibroblasts. Science, 280, 590-592.
31. Paull, T.T. & Gellert, M. (1999) Nbs1 potentiates ATP-driven DNA unwinding and endonuclease cleavage by the Mre11/Rad50 complex. Genes Dev., 13, 1276-1288.
32. Paull, T.T., Rogakou, E.P., Yamazaki, V., Kirchgessner, C.U., Gellert, M. & Bonner, W.M. (2000) A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr. Biol., 10, 886-895.
33. Redon, C., Pilch, D.R., Rogakou, E.P., Orr, A.H., Lowndes, N.F. & Bonner, W.M. (2003) Yeast histone 2A serine 129 is essential for the efficient repair of checkpoint-blind DNA damage. EMBO Rep., 4, 1-7.
34. Rogakou, E.P., Pilch, D.R., Orr, A.H., Ivanova, V.S. & Bonner, W.M. (1998) DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J. Biol. Chem., 273, 5858-68.
35. Rogakou, E.P., Boon, C., Redon, C. & Bonner, W.M. (1999) Megabase chromatin domains involved in DNA double-strand breaks in vivo. J. Cell Biol., 146, 905-916.
36. Shiloh, Y. (2003) ATM and related protein kinases: safeguarding genome integrity. Nature Rev. Cancer, 3, 155-168.
37. Soulier, J. & Lowndes, N.F. (1999) The BRCT domain of the S. cerevisiae checkpoint protein Rad9 mediates a Rad9-Rad9 interaction after DNA damage. Curr. Biol., 9, 551-554.
38. Stewart, G.S., Wang, B., Bignell, C.R., Taylor, A.M. & Elledge, S.J. (2003) MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature, 421, 961-966.
39. Stracker, T.H., Carson, C.T. & Weitzman, M.D. (2002) Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex. Nature, 418, 348-352.
40. Sugawara, N. & Haber, J.F. (1992) Characterization of double-strand break-induced recombination: homology requirements and single-stranded DNA formation. Mol. Cell. Biol., 12, 563-575.
41. van den Bosch, M., Lohman, P.H. & Pastink, A. (2002) DNA double-strand break repair by homologous recombination. Biol. Chem., 383, 873-892.
42. Wang, B., Matsuoka, S., Carpenter, P.B. & Elledge, S.J. (2002) 53BP1, a mediator of the DNA damage checkpoint. Science, 298, 1435-1438.
43. Williams, B.R., Mirzoeva, O.K., Morgan, W.F., Lin, J., Dunnick, W. & Petrini, J.H. (2002) A murine model of Nijmegen breakage syndrome. Curr. Biol., 12, 648-653.
44. Xiao, Y. & Weaver, D.T. (1997) Conditional gene targeted deletion by Cre recombinase demonstrates the requirement for the double-strand break repair Mre11 protein in murine embryonic stem cells. Nucleic Acids Res., 25, 2985-2991.
45. Yazdi, P.T., Wang, Y., Zhao, S., Patel, N., Lee, E.Y. & Qin, J. (2002) SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint. Genes Dev., 16, 571-582.
46. Zhao, S. et al. (2000) Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products. Nature, 405, 473-477.
47. Zhu, J., Petersen, S., Tessarollo, L. & Nussenzweig, A. (2001) Targeted disruption of the Nijmegen breakage syndrome gene NBS1 leads to early embryonic lethality in mice. Curr. Biol., 11, 105-109.