RAD51 binds BRCA2 at resected DNA DSBs

Stable Identifier
R-HSA-5693561
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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BRCA2 and RAD51 interact directly through the highly conserved BRCT repeats in BRCA2 (Venkitaraman 2002). CHEK1-mediated phosphorylation of BRCA2 (at threonine residue T3387) and RAD51 (at threonine residue T309) facilitates their binding (Sorensen et al. 2005, Bahassi et al. 2008). One BRCA2 can bind up to six RAD51 molecules, thus playing an important role in RAD51 nucleation at the dsDNA-ssDNA junction created by resection of DNA double strand breaks (DSBs) (Liu et al. 2010, Thorslund et al. 2010, Jensen et al. 2010). After the nucleation step, additional RAD51 molecules bind the ssDNA and multimerize, forming RAD51 nucleoprotein filaments (Yang et al. 2005). BRCA2-mediated RAD51 loading displaces the RPA complex from 3' overhanging ssDNA at DSBs (Sugiyama et al. 1997, Jensen et al. 2010), presumably with other RPA-bound proteins, such as ATR:ATRIP and complexes involved in ATR catalytic activation.

Literature References
PubMed ID Title Journal Year
9065463 A single-stranded DNA-binding protein is needed for efficient presynaptic complex formation by the Saccharomyces cerevisiae Rad51 protein

Sugiyama, T, Zaitseva, EM, Kowalczykowski, SC

J. Biol. Chem. 1997
20729858 The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA

Thorslund, T, McIlwraith, MJ, Compton, SA, Lekomtsev, S, Petronczki, M, Griffith, JD, West, SC

Nat. Struct. Mol. Biol. 2010
11832208 Cancer susceptibility and the functions of BRCA1 and BRCA2

Venkitaraman, AR

Cell 2002
18317453 The checkpoint kinases Chk1 and Chk2 regulate the functional associations between hBRCA2 and Rad51 in response to DNA damage

Bahassi, EM, Ovesen, JL, Riesenberg, AL, Bernstein, WZ, Hasty, PE, Stambrook, PJ

Oncogene 2008
15703751 The BRCA2 homologue Brh2 nucleates RAD51 filament formation at a dsDNA-ssDNA junction

Yang, H, Li, Q, Fan, J, Holloman, WK, Pavletich, NP

Nature 2005
15665856 The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair

Sørensen, CS, Hansen, LT, Dziegielewski, J, Syljuåsen, RG, Lundin, C, Bartek, J, Helleday, T

Nat. Cell Biol. 2005
20729832 Purified human BRCA2 stimulates RAD51-mediated recombination

Jensen, RB, Carreira, A, Kowalczykowski, SC

Nature 2010
20729859 Human BRCA2 protein promotes RAD51 filament formation on RPA-covered single-stranded DNA

Liu, J, Doty, T, Gibson, B, Heyer, WD

Nat. Struct. Mol. Biol. 2010
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