Reactome | D-loop formation mediated by PALB2, BRCA2 and RAD51

D-loop formation mediated by PALB2, BRCA2 and RAD51

Stable Identifier

R-HSA-5693620

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm, chromosome

Synonyms

Strand exchange/Branch migration mediated by PALB2, BRCA2 and RAD51

ReviewStatus

5/5

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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)
        
        D-loop formation mediated by PALB2, BRCA2 and RAD51 (Homo sapiens)

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D-loop formation mediated by PALB2, BRCA2 and RAD51

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A D-loop structure is formed when complementary duplex DNA (sister chromatid) is progressively invaded by the RAD51 nucleoprotein filament, with base pairing of the invading ssDNA and the complementary sister chromatid DNA strand (Sung et al. 2003). PALB2, RAD54, RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3), and RAD51AP1 synergistically stimulate RAD51 recombinase activity, thus enhancing RAD51-mediated strand exchange and promoting the formation of D-loop structures. PALB2 simultaneously interacts with RAD51, BRCA2 and RAD51AP1 (Modesti et al. 2007, Wiese et al. 2007, Buisson et al. 2010, Dray et al. 2010). The direct BRCA1 interaction with PALB2 helps to fine-tune the localization of BRCA2 and RAD51 at DNA double-strand breaks (DSBs) (Zhang et al. 2009, Sy et al. 2009). Phosphorylation of PALB2 by ATR on serine residue S59 promotes BRCA1-PALB2 interaction and the localization of PALB2 to DNA damage sites (Buisson et al. 2017).

Literature References

PubMed ID	Title	Journal	Year
20871616	Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2 Dray, E, Etchin, J, Wiese, C, Saro, D, Williams, GJ, Hammel, M, Yu, X, Galkin, VE, Liu, D, Tsai, MS, Sy, SM, Schild, D, Egelman, E, Chen, J, Sung, P	Nat. Struct. Mol. Biol.	2010
19268590	PALB2 links BRCA1 and BRCA2 in the DNA-damage response Zhang, F, Ma, J, Wu, J, Ye, L, Cai, H, Xia, B, Yu, X	Curr. Biol.	2009
19369211	PALB2 is an integral component of the BRCA complex required for homologous recombination repair Sy, SM, Huen, MS, Chen, J	Proc Natl Acad Sci U S A	2009
17996711	Promotion of homologous recombination and genomic stability by RAD51AP1 via RAD51 recombinase enhancement Wiese, C, Dray, E, Groesser, T, San Filippo, J, Shi, I, Collins, DW, Tsai, MS, Williams, GJ, Rydberg, B, Sung, P, Schild, D	Mol. Cell	2007
12912992	Rad51 recombinase and recombination mediators. Sung, P, Krejci, L, Van Komen, S, Sehorn, MG	J Biol Chem	2003
20871615	Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination Buisson, R, Dion-Côté, AM, Coulombe, Y, Launay, H, Cai, H, Stasiak, AZ, Stasiak, A, Xia, B, Masson, JY	Nat. Struct. Mol. Biol.	2010
28089683	Coupling of Homologous Recombination and the Checkpoint by ATR Buisson, R, Niraj, J, Rodrigue, A, Ho, CK, Kreuzer, J, Foo, TK, Hardy, EJ, Dellaire, G, Haas, W, Xia, B, Masson, JY, Zou, L	Mol Cell	2017
17996710	RAD51AP1 is a structure-specific DNA binding protein that stimulates joint molecule formation during RAD51-mediated homologous recombination Modesti, M, Budzowska, M, Baldeyron, C, Demmers, JA, Ghirlando, R, Kanaar, R	Mol. Cell	2007