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哺乳动物Mre11在经典和替代非同源末端连接中的作用。

Role of mammalian Mre11 in classical and alternative nonhomologous end joining.

作者信息

Xie Anyong, Kwok Amy, Scully Ralph

机构信息

Department of Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

出版信息

Nat Struct Mol Biol. 2009 Aug;16(8):814-8. doi: 10.1038/nsmb.1640. Epub 2009 Jul 26.

DOI:10.1038/nsmb.1640
PMID:19633669
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2730592/
Abstract

The mammalian Mre11-Rad50-Nbs1 (MRN) complex coordinates double-strand break signaling with repair by homologous recombination and is associated with the H2A.X chromatin response to double-strand breaks, but its role in nonhomologous end joining (NHEJ) is less clear. Here we show that Mre11 promotes efficient NHEJ in both wild-type and Xrcc4(-/-) mouse embryonic stem cells. Depletion of Mre11 reduces the use of microhomology during NHEJ in Xrcc4(+/+) cells and suppresses end resection in Xrcc4(-/-) cells, revealing specific roles for Mre11 in both classical and alternative NHEJ. The NHEJ function of Mre11 is independent of H2A.X. We propose a model in which both enzymatic and scaffolding functions of Mre11 cooperate to support mammalian NHEJ.

摘要

哺乳动物的Mre11-Rad50-Nbs1（MRN）复合物通过同源重组协调双链断裂信号与修复，并与H2A.X染色质对双链断裂的反应相关，但它在非同源末端连接（NHEJ）中的作用尚不清楚。在这里，我们表明Mre11在野生型和Xrcc4（-/-）小鼠胚胎干细胞中均促进高效的NHEJ。Mre11的缺失减少了Xrcc4（+/+）细胞在NHEJ过程中对微同源性的利用，并抑制了Xrcc4（-/-）细胞中的末端切除，揭示了Mre11在经典和替代NHEJ中的特定作用。Mre11的NHEJ功能独立于H2A.X。我们提出了一个模型，其中Mre11的酶促和支架功能协同支持哺乳动物的NHEJ。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/349b/2730592/b82934576323/nihms-125911-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/349b/2730592/72f33f6f7215/nihms-125911-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/349b/2730592/85a9b6e5a3d1/nihms-125911-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/349b/2730592/59f273f87b33/nihms-125911-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/349b/2730592/b82934576323/nihms-125911-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/349b/2730592/72f33f6f7215/nihms-125911-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/349b/2730592/85a9b6e5a3d1/nihms-125911-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/349b/2730592/59f273f87b33/nihms-125911-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/349b/2730592/b82934576323/nihms-125911-f0004.jpg

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