Reactome | EXO1 or DNA2 in complex with BLM or WRN binds initially resected DNA DSBs along with BRIP1 recruitment

EXO1 or DNA2 in complex with BLM or WRN binds initially resected DNA DSBs along with BRIP1 recruitment

Stable Identifier

R-HSA-5685985

Type

Reaction

Species

Homo sapiens

Compartment

nucleoplasm

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EXO1 or DNA2 in complex with BLM or WRN binds initially resected DNA DSBs along with BRIP1 recruitment

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After the initial resection of DNA double-strand breaks (DSBs) by MRE11A and RBBP8 (CtIP), which creates short 3' ssDNA overhangs, a DNA exonuclease EXO1 or a DNA endonuclease DNA2 is recruited to perform long-range resection of DNA DSBs. The redundant function of EXO1 and DNA2 in resection of DNA DSBs is conserved in yeast (Zhu et al. 2008). BLM, the Bloom syndrome helicase, acts as an activator of DNA2 catalytic activity (Nimonkar et al. 2011) and increases affinity of EXO1 for DNA ends (Nimonkar et al. 2008). BLM directly interacts with the MRN complex, which can assist recruitment of either DNA2 or EXO1 to DNA DSBs (Nimonkar et al. 2011). EXO1 can also be recruited to DNA DSBs through its interaction with RBBP8 (CtIP) (Eid et al. 2010, Nimonkar et al. 2011). Another DNA helicase, WRN (Werner syndrome helicase) can function redundantly with BLM to facilitate/activate EXO1- or DNA2-mediated long range resection of DNA DSBs (Sturzenegger et al. 2014).

A DNA helicase BRIP1 (also known as BACH1 or FANCJ) is recruited to DNA DSBs through its interaction with BRCA1 (Cantor et al. 2001) and BLM (Suhasini et al. 2011, Suhasini and Brosh 2012). BRIP1 promotes DNA end processing events that stimulate recruitment of the RPA complex and RAD51 (Xie et al. 2012). The interaction with BRCA1 requires BRIP1 to be phosphorylated on serine residue S990 in a cell cycle-dependent manner (Yu et al. 2003). BRIP1 also has to be acetylated on lysine residue K1249 to be functional (Xie et al. 2012).

Literature References

PubMed ID	Title	Journal	Year
16153896	BACH1 is critical for homologous recombination and appears to be the Fanconi anemia gene product FANCJ Zhang, F, Powell, S, Cantor, SB, Zhang, J, Litman, R, Andreassen, PR, Jin, Z, Peng, M	Cancer Cell	2005
18971343	Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair Modrich, P, Ozsoy, AZ, Nimonkar, AV, Genschel, J, Kowalczykowski, SC	Proc. Natl. Acad. Sci. U.S.A.	2008
18805091	Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends Shim, EY, Ira, G, Zhu, Z, Lee, SE, Chung, WH	Cell	2008
14576433	The BRCT domain is a phospho-protein binding domain Mer, G, Chini, CC, He, M, Chen, J, Yu, X	Science	2003
11301010	BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function Lane, WS, Sgroi, DC, Drapkin, R, Livingston, DM, Bell, DW, Grossman, S, Kass, EM, Haber, DA, Wahrer, DC, Cantor, SB, Ganesan, S	Cell	2001
22024395	Fanconi anemia and Bloom's syndrome crosstalk through FANCJ-BLM helicase interaction Suhasini, AN, Brosh, RM	Trends Genet.	2012
21325134	BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair Modrich, P, Polaczek, P, Wyman, C, Nimonkar, AV, Campbell, JL, Genschel, J, Kinoshita, E, Kowalczykowski, SC	Genes Dev.	2011
21052091	DNA end resection by CtIP and exonuclease 1 prevents genomic instability Peña-Diaz, J, El-Shemerly, M, Steger, M, Valtorta, E, Sartori, AA, Ferrari, S, Eid, W, König, C, Ferretti, LP	EMBO Rep.	2010
22792074	FANCJ/BACH1 acetylation at lysine 1249 regulates the DNA damage response Quan, S, Cantor, SB, Guillemette, S, Maniatis, S, Xie, J, Shaffer, SA, Venkatesh, A, Wu, Y, Brosh, RM, Peng, M	PLoS Genet.	2012
25122754	DNA2 cooperates with the WRN and BLM RecQ helicases to mediate long-range DNA end resection in human cells Pinto, C, Burdova, K, Sturzenegger, A, Janscak, P, Kanagaraj, R, Cejka, P, Levikova, M	J. Biol. Chem.	2014
21240188	Interaction between the helicases genetically linked to Fanconi anemia group J and Bloom's syndrome Rawtani, NA, Hickson, ID, North, PS, Cantor, SB, Mosedale, G, Sommers, JA, Suhasini, AN, Wu, Y, Brosh, RM, Sharma, S	EMBO J.	2011