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Cited by 517

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Microhomology-mediated End Joining and Homologous Recombination share the initial end resection step to repair DNA double-strand breaks in mammalian cells

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Truong, Lan N., Li, Yongjiang, Shi, Linda Z., Hwang, Patty Yi-Hwa, He, Jing, Wang, Hailong, Razavian, Niema, Berns, Michael W., Wu, Xiaohua·2013·Proceedings of the National Academy of Sciences

Abstract

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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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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CoChat. (2026). Citation check: Microhomology-mediated End Joining and Homologous Recombination share the initial end resection step to repair DNA double-strand breaks in mammalian cells. https://app.cochat.ai/papers/10.1073/pnas.1213431110
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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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