The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Microhomology-mediated End Joining and Homologous Recombination share the initial end resection step to repair DNA double-strand breaks in mammalian cells
Open accessAbstract
Microhomology-mediated end joining (MMEJ) is a major pathway for Ku-independent alternative nonhomologous end joining, which contributes to chromosomal translocations and telomere fusions, but the underlying mechanism of MMEJ in mammalian cells is not well understood. In this study, we demonstrated that, distinct from Ku-dependent classical nonhomologous end joining, MMEJ—even with very limited end resection—requires cyclin-dependent kinase activities and increases significantly when cells enter S phase. We also showed that MMEJ shares the initial end resection step with homologous recombination (HR) by requiring meiotic recombination 11 homolog A (Mre11) nuclease activity, which is needed for subsequent recruitment of Bloom syndrome protein (BLM) and exonuclease 1 (Exo1) to DNA double-strand breaks (DSBs) to promote extended end resection and HR. MMEJ does not require S139-phosphorylated histone H2AX (γ-H2AX), suggesting that initial end resection likely occurs at DSB ends. Using a MMEJ and HR competition repair substrate, we demonstrated that MMEJ with short end resection is used in mammalian cells at the level of 10–20% of HR when both HR and nonhomologous end joining are available. Furthermore, MMEJ is used to repair DSBs generated at collapsed replication forks. These studies suggest that MMEJ not only is a backup repair pathway in mammalian cells, but also has important physiological roles in repairing DSBs to maintain cell viability, especially under genomic stress.
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Cites
The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway
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Mechanisms of change in gene copy number
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ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks
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Sgs1 Helicase and Two Nucleases Dna2 and Exo1 Resect DNA Double-Strand Break Ends
Zhu, Z., Chung, W.-H., Shim, E. Y., Lee, S. E., & Ira, G. (2008) · Cell · doi:10.1016/j.cell.2008.08.037 · Cited by 1,051
MMEJ repair of double-strand breaks (director’s cut): deleted sequences and alternative endings
McVey, M., & Lee, S. E. (2008) · Trends in Genetics · doi:10.1016/j.tig.2008.08.007 · Cited by 986
Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis
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Alternative-NHEJ Is a Mechanistically Distinct Pathway of Mammalian Chromosome Break Repair
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Metadata
- Authors
- Truong, L. N., Li, Y., Shi, L. Z., Hwang, P. Y.-H., He, J., Wang, H., Razavian, N., Berns, M. W., & Wu, X.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2013-04-22
- Volume
- 110
- Issue
- 19
- Pages
- 7720-7725
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2007321086
- Cited by
- 517
- References
- 51
- FWCI
- 16.68
- Type
- journal article
- Language
- en
- Open access
- green
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- Truong, L. N., Li, Y., Shi, L. Z., Hwang, P. Y.-H., He, J., Wang, H., Razavian, N., Berns, M. W., & Wu, X. (2013). Microhomology-mediated End Joining and Homologous Recombination share the initial end resection step to repair DNA double-strand breaks in mammalian cells. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1213431110
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