Cited by 636DNA Repair MechanismsCRISPR and Genetic EngineeringPARP inhibition in cancer therapy

Microhomology-Mediated End Joining: A Back-up Survival Mechanism or Dedicated Pathway?

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Sfeir, Agnel, Symington, Lorraine S.·2015·Trends in Biochemical Sciences

Abstract

DNA double-strand breaks (DSBs) disrupt the continuity of chromosomes and their repair by error-free mechanisms is essential to preserve genome integrity. Microhomology-mediated end joining (MMEJ) is an error-prone repair mechanism that involves alignment of microhomologous sequences internal to the broken ends before joining, and is associated with deletions and insertions that mark the original break site, as well as chromosome translocations. Whether MMEJ has a physiological role or is simply a back-up repair mechanism is a matter of debate. Here we review recent findings pertaining to the mechanism of MMEJ and discuss its role in normal and cancer cells.

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Crossref · 10.1016/j.tibs.2015.08.006

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  • HRD tumors are dependent on alternative error-prone pathways including MMEJ, resulting in a characteristic mutational footprint across the genome that can be used to detect HRD regardless of the underlying cause.

    “For the repair of DSBs, HRD tumors are dependent on alternative more error-prone pathways including microhomology mediated end-joining (MMEJ)7, resulting in a characteristic mutational footprint across the genome that can be used to detect HRD regardless of the underlying cause (whether genetic or epigenetic).”

    From Pan-cancer landscape of homologous recombination deficiency. (2020) · cites this paper as [7]

    The “MMEJ and cancer” section reports rearrangements consistent with MMEJ in HR-deficient cancers, and the Concluding remarks say MMEJ seems to become essential in HR-defective backgrounds. The source thus supports the connection but hedges the asserted dependence; it does not establish that a genome-wide mutational footprint can detect HRD regardless of genetic or epigenetic cause. Page numbers were not available in our copy. (LLM, conf=0.86)

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Authors
Sfeir, A., & Symington, L. S.
Affiliations
  • NYU Langone Health (US)
  • Columbia University Irving Medical Center (US)
Corresponding author
  • Sfeir, Agnel
  • Symington, Lorraine S.
Venue
Trends in Biochemical Sciences
Publisher
Elsevier BV
Published
2015-11
Volume
40
Issue
11
Pages
701-714
ISSN
0968-0004 (ISSN-L)
OpenAlex
W2203229763
Cited by
636
References
98
Citations by year
2026: 49 · 2025: 55 · 2024: 66 · 2023: 71 · 2022: 61 · 2021: 81 · 2020: 64 · 2019: 58 · 2018: 48 · 2017: 44 · 2016: 39
FWCI
4.23
Type
journal article
Language
en
Open access
Locations
  • Trends in Biochemical Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • U.S. Bureau of Land Management
  • National Cancer Institute (P01CA174653, DP2CA195767)
  • National Institute of General Medical Sciences (R01GM041784)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK102562)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
Keywords
microhomology-mediated end joining, DNA double-strand break repair, error-prone DNA repair, genome stability, microhomology, chromosomal translocation, indels, cancer cells, DNA repair pathways
MeSH terms
Humans, Neoplasms, DNA End-Joining Repair

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