BRCA1 and Its Toolbox for the Maintenance of Genome Integrity

Overview

Journal Nat Rev Mol Cell Biol

Specialties Cell Biology
Molecular Biology

Date 2009 Dec 24

PMID 20029420

Citations 292

Authors

Michael S Y Huen

Shirley M H Sy

Junjie Chen

Affiliations

Soon will be listed here.

Abstract

The breast and ovarian cancer type 1 susceptibility protein (BRCA1) has pivotal roles in the maintenance of genome stability. Studies support that BRCA1 exerts its tumour suppression function primarily through its involvement in cell cycle checkpoint control and DNA damage repair. In addition, recent proteomic and genetic studies have revealed the presence of distinct BRCA1 complexes in vivo, each of which governs a specific cellular response to DNA damage. Thus, BRCA1 is emerging as the master regulator of the genome through its ability to execute and coordinate various aspects of the DNA damage response.

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References

Xia B, Dorsman J, Ameziane N, de Vries Y, Rooimans M, Sheng Q . Fanconi anemia is associated with a defect in the BRCA2 partner PALB2. Nat Genet. 2007; 39(2):159-61. DOI: 10.1038/ng1942. View

Chen L, Nievera C, Lee A, Wu X . Cell cycle-dependent complex formation of BRCA1.CtIP.MRN is important for DNA double-strand break repair. J Biol Chem. 2008; 283(12):7713-20. DOI: 10.1074/jbc.M710245200. View

Yarden R, Brody L . BRCA1 interacts with components of the histone deacetylase complex. Proc Natl Acad Sci U S A. 1999; 96(9):4983-8. PMC: 21803. DOI: 10.1073/pnas.96.9.4983. View

Thorslund T, West S . BRCA2: a universal recombinase regulator. Oncogene. 2007; 26(56):7720-30. DOI: 10.1038/sj.onc.1210870. View

Celeste A, Difilippantonio S, Difilippantonio M, Fernandez-Capetillo O, Pilch D, Sedelnikova O . H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell. 2003; 114(3):371-383. PMC: 4737479. DOI: 10.1016/s0092-8674(03)00567-1. View

Yu X, Chini C, He M, Mer G, Chen J . The BRCT domain is a phospho-protein binding domain. Science. 2003; 302(5645):639-42. DOI: 10.1126/science.1088753. View

Yarden R, Pardo-Reoyo S, Sgagias M, Cowan K, Brody L . BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage. Nat Genet. 2002; 30(3):285-9. DOI: 10.1038/ng837. View

Joukov V, Chen J, Fox E, Green J, Livingston D . Functional communication between endogenous BRCA1 and its partner, BARD1, during Xenopus laevis development. Proc Natl Acad Sci U S A. 2001; 98(21):12078-83. PMC: 59770. DOI: 10.1073/pnas.211427098. View

Fernandez-Capetillo O, Chen H, Celeste A, Ward I, Romanienko P, Morales J . DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1. Nat Cell Biol. 2002; 4(12):993-7. DOI: 10.1038/ncb884. View

10.

Feng L, Huang J, Chen J . MERIT40 facilitates BRCA1 localization and DNA damage repair. Genes Dev. 2009; 23(6):719-28. PMC: 2661609. DOI: 10.1101/gad.1770609. View

11.

Christensen D, Brzovic P, Klevit R . E2-BRCA1 RING interactions dictate synthesis of mono- or specific polyubiquitin chain linkages. Nat Struct Mol Biol. 2007; 14(10):941-8. DOI: 10.1038/nsmb1295. View

12.

Wang B, Matsuoka S, Ballif B, Zhang D, Smogorzewska A, Gygi S . Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science. 2007; 316(5828):1194-8. PMC: 3573690. DOI: 10.1126/science.1139476. View

13.

Hofmann R, Pickart C . Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell. 1999; 96(5):645-53. DOI: 10.1016/s0092-8674(00)80575-9. View

14.

Goldberg M, Stucki M, Falck J, DAmours D, Rahman D, Pappin D . MDC1 is required for the intra-S-phase DNA damage checkpoint. Nature. 2003; 421(6926):952-6. DOI: 10.1038/nature01445. View

15.

Foray N, Marot D, Gabriel A, Randrianarison V, Carr A, Perricaudet M . A subset of ATM- and ATR-dependent phosphorylation events requires the BRCA1 protein. EMBO J. 2003; 22(11):2860-71. PMC: 156770. DOI: 10.1093/emboj/cdg274. View

16.

Nishikawa H, Wu W, Koike A, Kojima R, Gomi H, Fukuda M . BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING heterodimer activity. Cancer Res. 2009; 69(1):111-9. DOI: 10.1158/0008-5472.CAN-08-3355. View

17.

Shen X, Do H, Li Y, Chung W, Tomasz M, de Winter J . Recruitment of fanconi anemia and breast cancer proteins to DNA damage sites is differentially governed by replication. Mol Cell. 2009; 35(5):716-23. PMC: 2758766. DOI: 10.1016/j.molcel.2009.06.034. View

18.

Xia B, Sheng Q, Nakanishi K, Ohashi A, Wu J, Christ N . Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol Cell. 2006; 22(6):719-729. DOI: 10.1016/j.molcel.2006.05.022. View

19.

Peng M, Litman R, Xie J, Sharma S, Brosh Jr R, Cantor S . The FANCJ/MutLalpha interaction is required for correction of the cross-link response in FA-J cells. EMBO J. 2007; 26(13):3238-49. PMC: 1914102. DOI: 10.1038/sj.emboj.7601754. View

20.

Xia Y, Pao G, Chen H, Verma I, Hunter T . Enhancement of BRCA1 E3 ubiquitin ligase activity through direct interaction with the BARD1 protein. J Biol Chem. 2002; 278(7):5255-63. DOI: 10.1074/jbc.M204591200. View