Molding BRCA2 Function Through Its Interacting Partners

Overview

Journal Cell Cycle

Specialty Cell Biology

Date 2015 Nov 15

PMID 26566862

Citations 16

Authors

Juan S Martinez

Celine Baldeyron

Aura Carreira

Affiliations

Soon will be listed here.

Abstract

The role of the tumor suppressor BRCA2 has been shaped over 2 decades thanks to the discovery of its protein and nucleic acid partners, biochemical and structural studies of the protein, and the functional evaluation of germline variants identified in breast cancer patients. Yet, the pathogenic and functional effect of many germline mutations in BRCA2 remains undetermined, and the heterogeneity of BRCA2-associated tumors challenges the identification of causative variants that drive tumorigenesis. In this review, we propose an overview of the established and emerging interacting partners and functional pathways attributed to BRCA2, and we speculate on how variants altering these functions may contribute to cancer susceptibility.

Citing Articles

The impact of pathogenic tumor mutation status on high grade serous epithelial ovarian cancer survival outcome: A multicenter study from Indonesia.

Sutrisno S, Marlina D, Tjandraprawira K, Adriansyah P SAGE Open Med. 2024; 12:20503121241299849.

PMID: 39575313 PMC: 11580090. DOI: 10.1177/20503121241299849.

Prediction of and Variants with Conflicting Clinical Interpretation in a Cohort of Breast Cancer Patients.

Stella S, Vitale S, Massimino M, Martorana F, Tornabene I, Tomarchio C Genes (Basel). 2024; 15(7).

PMID: 39062721 PMC: 11276437. DOI: 10.3390/genes15070943.

Identification of a large intra-exonic deletion in exon 18 in a pancreatic ductal adenocarcinoma.

Debbabi I, Vacher S, Neuzillet C, Cros J, Revillon F, Petitalot A Ther Adv Med Oncol. 2023; 15:17588359221146132.

PMID: 36700131 PMC: 9869184. DOI: 10.1177/17588359221146132.

Assessing the Variations in Breast/Ovarian Cancer Risk for Chinese Carriers.

Li A, Hao S, Luo J, Zi Y, Lan Z, Zhou T J Oncol. 2022; 2022:9390539.

PMID: 35378767 PMC: 8976609. DOI: 10.1155/2022/9390539.

Guardians of the Genome: BRCA2 and Its Partners.

Le H, Heyer W, Liu J Genes (Basel). 2021; 12(8).

PMID: 34440403 PMC: 8394001. DOI: 10.3390/genes12081229.

References

Deans A, West S . DNA interstrand crosslink repair and cancer. Nat Rev Cancer. 2011; 11(7):467-80. PMC: 3560328. DOI: 10.1038/nrc3088. View

Carreira A, Kowalczykowski S . Two classes of BRC repeats in BRCA2 promote RAD51 nucleoprotein filament function by distinct mechanisms. Proc Natl Acad Sci U S A. 2011; 108(26):10448-53. PMC: 3127913. DOI: 10.1073/pnas.1106971108. View

Menzel T, Nahse-Kumpf V, Nedergaard Kousholt A, Klein D, Lund-Andersen C, Lees M . A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance. EMBO Rep. 2011; 12(7):705-12. PMC: 3128973. DOI: 10.1038/embor.2011.99. View

Lee M, Daniels M, Garnett M, Venkitaraman A . A mitotic function for the high-mobility group protein HMG20b regulated by its interaction with the BRC repeats of the BRCA2 tumor suppressor. Oncogene. 2011; 30(30):3360-9. PMC: 3145889. DOI: 10.1038/onc.2011.55. View

Muller D, Rouleau E, Schultz I, Caputo S, Lefol C, Bieche I . An entire exon 3 germ-line rearrangement in the BRCA2 gene: pathogenic relevance of exon 3 deletion in breast cancer predisposition. BMC Med Genet. 2011; 12:121. PMC: 3198910. DOI: 10.1186/1471-2350-12-121. View

Shahid T, Soroka J, Kong E, Malivert L, McIlwraith M, Pape T . Structure and mechanism of action of the BRCA2 breast cancer tumor suppressor. Nat Struct Mol Biol. 2014; 21(11):962-968. PMC: 4222816. DOI: 10.1038/nsmb.2899. View

Raghunandan M, Chaudhury I, Kelich S, Hanenberg H, Sobeck A . FANCD2, FANCJ and BRCA2 cooperate to promote replication fork recovery independently of the Fanconi Anemia core complex. Cell Cycle. 2015; 14(3):342-53. PMC: 4614542. DOI: 10.4161/15384101.2014.987614. View

Zhao W, Vaithiyalingam S, San Filippo J, Maranon D, Jimenez-Sainz J, Fontenay G . Promotion of BRCA2-Dependent Homologous Recombination by DSS1 via RPA Targeting and DNA Mimicry. Mol Cell. 2015; 59(2):176-87. PMC: 4506714. DOI: 10.1016/j.molcel.2015.05.032. View

Carreira A, Hilario J, Amitani I, Baskin R, Shivji M, Venkitaraman A . The BRC repeats of BRCA2 modulate the DNA-binding selectivity of RAD51. Cell. 2009; 136(6):1032-43. PMC: 2669112. DOI: 10.1016/j.cell.2009.02.019. View

10.

Zhang F, Ma J, Wu J, Ye L, Cai H, Xia B . PALB2 links BRCA1 and BRCA2 in the DNA-damage response. Curr Biol. 2009; 19(6):524-9. PMC: 2750839. DOI: 10.1016/j.cub.2009.02.018. View

11.

Ayoub N, Rajendra E, Su X, Jeyasekharan A, Mahen R, Venkitaraman A . The carboxyl terminus of Brca2 links the disassembly of Rad51 complexes to mitotic entry. Curr Biol. 2009; 19(13):1075-85. PMC: 2719694. DOI: 10.1016/j.cub.2009.05.057. View

12.

Oliver A, Swift S, Lord C, Ashworth A, Pearl L . Structural basis for recruitment of BRCA2 by PALB2. EMBO Rep. 2009; 10(9):990-6. PMC: 2750052. DOI: 10.1038/embor.2009.126. View

13.

Zhou Q, Mazloum N, Mao N, Kojic M, Holloman W . Dss1 regulates interaction of Brh2 with DNA. Biochemistry. 2009; 48(50):11929-38. PMC: 2795026. DOI: 10.1021/bi901775j. View

14.

Lekomtsev S, Guizetti J, Pozniakovsky A, Gerlich D, Petronczki M . Evidence that the tumor-suppressor protein BRCA2 does not regulate cytokinesis in human cells. J Cell Sci. 2010; 123(Pt 9):1395-400. DOI: 10.1242/jcs.068015. View

15.

Chen C, Chen P, Zhong Q, Sharp Z, Lee W . Expression of BRC repeats in breast cancer cells disrupts the BRCA2-Rad51 complex and leads to radiation hypersensitivity and loss of G(2)/M checkpoint control. J Biol Chem. 1999; 274(46):32931-5. DOI: 10.1074/jbc.274.46.32931. View

16.

Spain B, Larson C, Shihabuddin L, Gage F, Verma I . Truncated BRCA2 is cytoplasmic: implications for cancer-linked mutations. Proc Natl Acad Sci U S A. 1999; 96(24):13920-5. PMC: 24166. DOI: 10.1073/pnas.96.24.13920. View

17.

Yu V, Koehler M, Steinlein C, Schmid M, Hanakahi L, van Gool A . Gross chromosomal rearrangements and genetic exchange between nonhomologous chromosomes following BRCA2 inactivation. Genes Dev. 2000; 14(11):1400-6. PMC: 316655. View

18.

Howlett N, Taniguchi T, Olson S, Cox B, Waisfisz Q, de Die-Smulders C . Biallelic inactivation of BRCA2 in Fanconi anemia. Science. 2002; 297(5581):606-9. DOI: 10.1126/science.1073834. View

19.

Yang H, Jeffrey P, Miller J, Kinnucan E, Sun Y, Thoma N . BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure. Science. 2002; 297(5588):1837-48. DOI: 10.1126/science.297.5588.1837. View

20.

Pellegrini L, Yu D, Lo T, Anand S, Lee M, Blundell T . Insights into DNA recombination from the structure of a RAD51-BRCA2 complex. Nature. 2002; 420(6913):287-93. DOI: 10.1038/nature01230. View