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

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 repai...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Vol. 80; no. 21; p. 4593
Main Authors: Patterson-Fortin, Jeffrey, D'Andrea, Alan D
Format: Journal Article
Language:English
Published: United States 01.11.2020
Subjects:
Animals
DNA Breaks, Double-Stranded
DNA End-Joining Repair
Humans
Neoplasms
ISSN:1538-7445, 1538-7445
Online Access:Get more information
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Summary: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.
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ISSN:1538-7445
1538-7445
DOI:10.1158/0008-5472.CAN-20-1672