End resection: a key step in homologous recombination and DNA double-strand break repair

Sijie Liu,Daochun Kong

doi:10.1007/s42764-020-00028-5

Abstract

DNA end resection in eukaryotes is a key step in DNA homologous recombination (HR) and HR-mediated DNA double-strand break (DSB) repair, in which DNA2, EXO1 and MRE11 endo- and exonucleases remove several kilobases from the 5′ terminus of the DNA with DSB, while the 3′ terminus remains intact. The end resection-generated 3′ single-stranded DNA (ssDNA) overhang is then coated by RAD51 for subsequent strand invasion. In the last two decades, great progress has been made in understanding the biochemical mechanisms of end resection, including the identification of various enzymes involved in this process. However, some important questions about this process remain to be resolved. In this review, we summarize the general process of end resection and discuss the implications of the most recent findings for understanding of the end resection machinery.

Highlights

Genomic DNA is frequently at risk of damages from a variety of physical or chemical hazards, such as ultraviolet (UV) radiation, ionizing radiation, and chemotherapy drugs, that trigger a diverse range of DNA lesions, including phosphodiester backbone breakage, inter-strand cross-linking, and base oxidation and reduction (Sancar et al 2004; Tubbs and Nussenzweig 2017; Ciccia and Elledge 2010)
We focus on the process of DNA end resection and its mechanism in eukaryotes
When doublestrand break (DSB) occur in chromatin DNA, these breaks must be immediately recognized by the cell; otherwise, further DNA damage, such as genetic loss, may occur

Summary

Introduction

Genomic DNA is frequently at risk of damages from a variety of physical or chemical hazards, such as ultraviolet (UV) radiation, ionizing radiation, and chemotherapy drugs, that trigger a diverse range of DNA lesions, including phosphodiester backbone breakage, inter-strand cross-linking, and base oxidation and reduction (Sancar et al 2004; Tubbs and Nussenzweig 2017; Ciccia and Elledge 2010). These DNA lesions can severely affect genomic integrity and the survival of living organisms. We focus on the process of DNA end resection and its mechanism in eukaryotes

DSB recognition

Processing DSB ends

Initiation of DNA end resection

Processing of DNA end resection

Termination of DNA end resection