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
Locations in the PathwayBrowser
Summation

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).

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Orthologous Events