DNA End Resection: Facts and Mechanisms

Abstract

DNA double-strand breaks (DSBs), which arise following exposure to a number of endogenous and exogenous agents, can be repaired by either the homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways in eukaryotic cells. A vital step in HR repair is DNA end resection, which generates a long 3' single-stranded DNA (ssDNA) tail that can invade the homologous DNA strand. The generation of 3' ssDNA is not only essential for HR repair, but also promotes activation of the ataxia telangiectasia and Rad3-related protein (ATR). Multiple factors, including the MRN/X complex, C-terminal-binding protein interacting protein (CtIP)/Sae2, exonuclease 1 (EXO1), Bloom syndrome protein (BLM)/Sgs1, DNA2 nuclease/helicase, and several chromatin remodelers, cooperate to complete the process of end resection. Here we review the basic machinery involved in DNA end resection in eukaryotic cells.

Keywords: Chromatin remodeling factors; DNA double-strand breaks; DNA end resection; Genome stability; Homologous recombination.

Figure 1

DNA-end resection occurs via a two-step process—resection initiation and resection extension Resection initiation is stimulated by SRCAP, CtIP, and the MRN complex. SMARCAD1 cooperates with EXO1 and BLM/DNA2 to promote resection extension. The figure is adapted from . ATR, ataxia telangiectasia and Rad3-related protein; BLM, Bloom syndrome protein; CtIP, C-terminal-binding protein interacting protein; EXO1, exonuclease 1; HR, homologous recombination; MRN, MRE11, RAD50, and nibrin; RPA, replication protein A; SMARCAD1, switch/sucrose non-fermentable (SWI/SNF)-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1; SRCAP, Snf2-related CREB-binding protein activator protein; ssDNA, single-stranded DNA.