التفاصيل البيبلوغرافية
| العنوان: |
Microhomology-mediated End Joining and Homologous Recombination share the initial end resection step to repair DNA double-strand breaks in mammalian cells. |
| المؤلفون: |
Truong, Lan N., Yongjiang Li, Shi, Linda Z., Patty Yi-Hwa Hwang, Jing He, Hailong Wang, Niema Razavian, Berns, Michael W., Xiaohua Wu |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 5/7/2013, Vol. 110 Issue 19, p7720-7725, 6p |
| مصطلحات موضوعية: |
HOMOLOGY (Biochemistry), DOUBLE-stranded RNA, TELOMERES, CYCLIN-dependent kinases, BLOOM syndrome, EXONUCLEASES |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
