Nature cell Biology：发现维持端粒长度重要分子

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来自华盛顿大学医学院放射线肿瘤学系，细胞生物与生理学系，国立癌症研究所人类癌症遗传研究实验室的研究者在Nature  cell  Biology上发表端粒的最新研究进展，文章标题为：Telomere  recombination  requires  the  MUS81  endonuclease。6 Y' S1 W) d/ r% _0 A

4 j7 W& c0 B1 l1 n3 n文章通讯作者是早年毕业于中国华西医科大的华盛顿大学医学院的助理教授杨钦（Qin  Yang，音译）和国立癌症研究所的Curtis  C.  Harris教授，Curtis  C.  Harris是癌症研究所的首席科学家，是P53领域的顶级科学家，其91年在Science发表的P53研究文章获得了3259次引用。文章第一作者是华盛顿大学医学院的曾思聪（Sicong  Zeng，音译），目前在中南大学生殖与干细胞研究所工作。
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杨钦所在的研究所主要研究癌症，据介绍，缺少端粒酶的癌细胞主要依赖ALT路径延长端粒。尽管很多的证据证实ALT是一个端粒重组的机制，但是其中的分子基础等一直不明确。
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本研究小组发现MUS81（一种DNA结构特异性的重组核酸内切酶）是维持人类ALT细胞端粒长度的重要分子。通过一系列的论证，研究者得出结论MUS81是维持细胞端粒长度的关键酶1 V1 d' G# i! k8 ?$ Q: U% [  m
推荐原始出处：
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Nat Cell Biol. 2009 Apr 12  |: E2 {- a8 z* W

: s1 k+ v. n- V; {Telomere recombination requires the MUS81 endonuclease.
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Zeng S, Xiang T, Pandita TK, Gonzalez-Suarez I, Gonzalo S, Harris CC, Yang Q- V  a/ V0 l# b3 f5 q  `( L  r
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[1] Department of Radiation Oncology, Washington University School of Medicine, 4511 Forest Park, St. Louis, MO 63108, USA. [2] Current address: Institute of Reproduction and Stem Cell Engineering, Central South University, Changsha, Hunan 410078, China.. r: t  c# O; f: q
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Telomerase-negative cancer cells maintain their telomeres through the alternative lengthening of telomeres (ALT) pathway. Although a growing body of evidence demonstrates that the ALT mechanism is a post-replicative telomere recombination process, molecular details of this pathway are largely unknown. Here we demonstrate that MUS81, a DNA structure specific recombination endonuclease, has a key role in the maintenance of telomeres in human ALT cells. We find that MUS81 specifically localizes to ALT-associated promyelocytic leukaemia (PML) nuclear bodies (APBs) and associates with telomeric DNA in ALT cells, which is enriched during the G2 phase of the cell cycle. Depletion of MUS81 results in the reduction of ALT-specific telomere recombination and leads to proliferation arrest of ALT cells. In addition, the endonuclease activity of MUS81 is required for recombination-based ALT cell survival, and the interaction of MUS81 with the telomeric repeat-binding factor TRF2 regulates this enzymatic activity, thereby maintaining telomere recombination. Thus, our results suggest that MUS81 is involved in the maintenance of ALT cell survival at least in part by homologous recombination of telomeres.

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