Reactome | Presynaptic phase of homologous DNA pairing and strand exchange

Presynaptic phase of homologous DNA pairing and strand exchange

Stable Identifier

R-HSA-5693616

DOI

10.3180/R-HSA-5693616.3

Type

Pathway

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

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DNA Repair (Homo sapiens)

- DNA Double-Strand Break Repair (Homo sapiens)
  - Homology Directed Repair (Homo sapiens)
    - HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) (Homo sapiens)
      - HDR through Homologous Recombination (HRR) (Homo sapiens)
        
        Homologous DNA Pairing and Strand Exchange (Homo sapiens)
        
        Presynaptic phase of homologous DNA pairing and strand exchange (Homo sapiens)

General

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The presynaptic phase of homologous DNA pairing and strand exchange during homologous recombination repair (HRR) begins with the displacement of RPA from ssDNA (Thompson and Limoli 2003) by the joint action of RAD51 and BRCA2. CHEK1-mediated phosphorylation of RAD51 and BRCA2 (Sorensen et al. 2005, Bahassi et al. 2008) is needed for BRCA2-mediated nucleation of RAD51 on 3'-ssDNA overhangs, RPA displacement and formation of RAD51 nucleofilaments (Yang et al. 2005, Jensen et al. 2010, Liu et al. 2010, Thorslund et al. 2010). Invasive RAD51 nucleofilaments are stabilized by the BCDX2 complex composed of RAD51B, RAD51C, RAD51D and XRCC2 (Masson et al. 2001, Chun et al. 2013, Amunugama et al. 2013).

Literature References

PubMed ID	Title	Journal	Year
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
	Eukaryotic DNA Damage Surveillance and Repair Caldecott, KW		2004
23149936	Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway Chun, J, Buechelmaier, ES, Powell, SN	Mol. Cell. Biol.	2013
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
11751635	Identification and purification of two distinct complexes containing the five RAD51 paralogs Masson, JY, Tarsounas, MC, Stasiak, AZ, Stasiak, A, Shah, R, McIlwraith, MJ, Benson, FE, West, SC	Genes Dev.	2001
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
23810717	The HsRAD51B-HsRAD51C stabilizes the HsRAD51 nucleoprotein filament Amunugama, R, Groden, J, Fishel, R	DNA Repair (Amst.)	2013
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