Regulation of pathway choice in DNA repair after double-strand breaks

Abstract

DNA damage signaling is a highly coordinated cellular process which is required for the removal of DNA lesions. Amongst the different types of DNA damage, double-strand breaks (DSBs) are the most harmful type of lesion that attenuates cellular proliferation. DSBs are repaired by two major pathways—homologous recombination (HR), and non-homologous end-joining (NHEJ) and in some cases by microhomology-mediated end-joining (MMEJ). Preference of the pathway depends on multiple parameters including site of the DNA damage, the cell cycle phase and topology of the DNA lesion. Deregulated repair response contributes to genomic instability resulting in a plethora of diseases including cancer. This review discusses the different molecular players of HR, NHEJ, and MMEJ pathways that control the switch among the different DSB repair pathways. We also highlight the various functions of chromatin modifications in modulating repair response and how deregulated DNA damage repair response may promote oncogenic transformation.