來自華盛頓大學(xué)醫(yī)學(xué)院放射線腫瘤學(xué)系,，細(xì)胞生物與生理學(xué)系,，國立癌癥研究所人類癌癥遺傳研究實(shí)驗(yàn)室的研究者在Nature cell Biology上發(fā)表端粒的最新研究進(jìn)展,，文章標(biāo)題為：Telomere recombination requires the MUS81 endonuclease,。
文章通訊作者是早年畢業(yè)于中國華西醫(yī)科大的華盛頓大學(xué)醫(yī)學(xué)院的助理教授楊欽（Qin Yang,，音譯）和國立癌癥研究所的Curtis C. Harris教授,，Curtis C. Harris是癌癥研究所的首席科學(xué)家,，是P53領(lǐng)域的頂級(jí)科學(xué)家,，其91年在Science發(fā)表的P53研究文章獲得了3259次引用。文章第一作者是華盛頓大學(xué)醫(yī)學(xué)院的曾思聰（Sicong Zeng，音譯）,，目前在中南大學(xué)生殖與干細(xì)胞研究所工作,。
楊欽所在的研究所主要研究癌癥，據(jù)介紹,，缺少端粒酶的癌細(xì)胞主要依賴ALT路徑延長端粒,。盡管很多的證據(jù)證實(shí)ALT是一個(gè)端粒重組的機(jī)制，但是其中的分子基礎(chǔ)等一直不明確,。
本研究小組發(fā)現(xiàn)MUS81（一種DNA結(jié)構(gòu)特異性的重組核酸內(nèi)切酶）是維持人類ALT細(xì)胞端粒長度的重要分子,。通過一系列的論證，研究者得出結(jié)論MUS81是維持細(xì)胞端粒長度的關(guān)鍵酶,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nat Cell Biol. 2009 Apr 12
Telomere recombination requires the MUS81 endonuclease.
Zeng S, Xiang T, Pandita TK, Gonzalez-Suarez I, Gonzalo S, Harris CC, Yang Q
[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.
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.
