Microhomology-Mediated End Joining: A Back-up Survival Mechanism or Dedicated Pathway?
Open accessAbstract
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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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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Self-citationMATSUZAKI, K., Terasawa, M., Iwasaki, D., et al. (2012) · Genes to Cells · doi:10.1111/j.1365-2443.2012.01602.x · Cited by 33 · see citing works
REV7/MAD2L2: the multitasking maestro emerges as a barrier to recombination
Sale, J. E. (2015) · The EMBO Journal · doi:10.15252/embj.201591697 · Cited by 22 · see citing works
Microhomology-Mediated Intron Loss during Metazoan Evolution
van Schendel, R., & Tijsterman, M. (2013) · Genome Biology and Evolution · doi:10.1093/gbe/evt088 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Richardson, C. D., Ray, G. J., DeWitt, M. A., Curie, G. L., & Corn, J. E. (2016) · Nature Biotechnology · doi:10.1038/nbt.3481 · Cited by 1,098 · see citing works
Shelterin-Mediated Telomere Protection
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The control of DNA repair by the cell cycle
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Highly efficient therapeutic gene editing of human hematopoietic stem cells
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Pan-cancer landscape of homologous recombination deficiency.
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“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).”
BackgroundDNA Repair Pathway Choices in CRISPR-Cas9-Mediated Genome Editing
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Allele-Specific Chromosome Removal after Cas9 Cleavage in Human Embryos
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Do DNA Double-Strand Breaks Drive Aging?
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Repair of DNA Double-Strand Breaks by the Nonhomologous End Joining Pathway
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Cas9-induced large deletions and small indels are controlled in a convergent fashion
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DNA double-strand breaks as drivers of neural genomic change, function, and disease
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Genetic Variation and Unintended Risk in the Context of Old and New Breeding Techniques
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Mitotic Recombination and Adaptive Genomic Changes in Human Pathogenic Fungi
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Evolution of prime editing systems: move forward to the treatment of hereditary diseases
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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)
- PMC
- PMC4638128
- OpenAlex
- W2203229763
- Semantic Scholar
- 0fb88ceaf5fddaceeaa34989ace2c2861600e6f8
- 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
- green
- www.ncbi.nlm.nih.gov
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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