Crosstalk between different DNA repair pathways for DNA double strand break repairs

•DNA double strand breaks are one of the most dangerous DNA damage.•There are at least four different DNA double strand break repair mechanisms.•Choice for DNA double strand break repair mechanisms depends on DNA end resection.•Mismatch repair enzymes, MSH2-MSH3 function in homologous recombination. DNA double strand breaks (DSBs) are the most threatening type of DNA lesions and must be repaired properly in order to inhibit severe diseases and cell death. There are four major repair pathways for DSBs: non-homologous end joining (NHEJ), homologous recombination (HR), single strand annealing (SSA) and alternative end joining (alt-EJ). Cells choose repair pathway depending on the cell cycle phase and the length of 3′ end of the DNA when DSBs are generated. Blunt and short regions of the 5′ or 3′ overhang DNA are repaired by NHEJ, which uses direct ligation or limited resection processing of the broken DNA end. In contrast, HR, SSA and alt-EJ use the resected DNA generated by the MRN (MRE11-RAD50-NBS1) complex and C-terminal binding protein interacting protein (CtIP) activated during the S and G2 phases. Here, we review recent findings on each repair pathway and the choice of repair mechanism and highlight the role of mismatch repair (MMR) protein in HR.