Exploiting the Microhomology-Mediated End-Joining Pathway in Cancer Therapy

Abstract

Repair of DNA double-strand breaks (DSB) is performed by two major pathways, homology-dependent repair and classical nonhomologous end-joining. Recent studies have identified a third pathway, microhomology-mediated end-joining (MMEJ). MMEJ has similarities to homology-dependent repair, in that repair is initiated with end resection, leading to single-stranded 3′ ends, which require microhomology upstream and downstream of the DSB. Importantly, the MMEJ pathway is commonly upregulated in cancers, especially in homologous recombination-deficient cancers, which display a distinctive mutational signature. Here, we review the molecular process of MMEJ as well as new targets and approaches exploiting the MMEJ pathway in cancer therapy.

Document Details

Document Type
Pub Defense Publication
Publication Date
Nov 01, 2020
Source ID
10.1158/0008-5472.can-20-1672

Entities

People

  • Alan D'Andrea
  • Jeffrey Patterson-fortin

Organizations

  • Dana–Farber Cancer Institute
  • National Institutes of Health
  • Stand Up to Cancer
  • United States Department of Defense

Tags

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Molecular Genetics
  • Personnel Management and Statistics in the Military and Department of Defense