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本帖最后由 细胞海洋 于 2010-4-16 18:12 编辑 + _1 W- T; f, K: ~& v
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转自生物谷：4月13日电美国研究人员最新发现，一种特殊的蛋白质可以有效修复严重受损的DNA（脱氧核糖核酸），这一发现有望帮助治疗因机体老化、DNA受损而导致的诸多疾病。
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0 D9 B5 ?5 X" p3 q' y' i) BDNA是人类主要的遗传物质，染色体由双链DNA分子和组蛋白所组成。生命科学研究普遍认为，随着机体老化，染色体内DNA会出现不同程度损伤，这是导致人体出现癌症以及其他一些与衰老有关疾病的关键因素。与此同时，机体自身也会尽力去修复受损DNA，但背后具体的机理人们尚不清楚。
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美国北卡罗来纳大学研究人员在最新一期英国《自然》杂志上发表报告说，他们研究发现，一种被称为Ku的蛋白质可以通过特殊方法有效修复一类严重的DNA损伤。
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! y! [6 A3 x' o# Y% ^参与研究的戴尔·拉姆斯登介绍说，在各种DNA损伤中，DNA双链断裂导致的整个染色体被破坏，是最难修复的一种。这类损伤发生时，构成DNA分子的基本单位——核苷酸可能受到了破坏。因此，此前科学家认为，这类DNA损伤根本无法精确修复。& T. D- _0 |4 p! r/ c
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而他们的最新研究却发现，Ku蛋白质可以完成这种高难度的修复工作。它首先定位DNA双链断裂处，然后能够精确地将出问题的核苷酸修复，最后再对整个染色体进行检查，“整个过程就好比在缝合伤口前首先清洗伤口并为其消毒”。/ E5 j& {& M0 l C- |6 O
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研究人员表示，他们希望在此基础上能够获得更多的有关DNA损伤修复的信息，进而能够寻找到与机体衰老相关疾病的新疗法。(生物谷Bioon.com)
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. F' @ a( j4 O s. \生物谷推荐原文出处：
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Nature doi:10.1038/nature08926+ p- a/ b+ V; I j: v7 N
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Ku is a 5′-dRP/AP lyase that excises nucleotide damage near broken ends% f7 o; v* S( C. U
Steven A. Roberts1, Natasha Strande1, Martin D. Burkhalter1, Christina Strom1, Jody M. Havener1, Paul Hasty2 & Dale A. Ramsden1! L6 W. W4 U- S: R
6 b0 p' I: @! `+ b1 Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, and Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA / ^$ {, `7 i/ c4 i3 T: Z
2 Department of Molecular Medicine and Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, Texas 78245, USA # Y- H7 m+ X$ f" j) ]
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Top of pageMammalian cells require non-homologous end joining (NHEJ) for the efficient repair of chromosomal DNA double-strand breaks1. A key feature of biological sources of strand breaks is associated nucleotide damage, including base loss (abasic or apurinic/apyrimidinic (AP) sites)2. At single-strand breaks, 5′-terminal abasic sites are excised by the 5′-deoxyribose-5-phosphate (5′-dRP) lyase activity of DNA polymerase?β (pol?β)3, 4, 5, 6: here we show, in vitro and in cells, that accurate and efficient repair by NHEJ of double-strand breaks with such damage similarly requires 5′-dRP/AP lyase activity. Classically defined NHEJ is moreover uniquely effective at coupling this end-cleaning step to joining in cells, helping to distinguish this pathway from otherwise robust alternative NHEJ pathways. The NHEJ factor Ku can be identified as an effective 5′-dRP/AP lyase. In a similar manner to other lyases7, Ku nicks DNA 3′ of an abasic site by a mechanism involving a Schiff-base covalent intermediate with the abasic site. We show by using cell extracts that Ku is essential for the efficient removal of AP sites near double-strand breaks and, consistent with this result, that joining of such breaks is specifically decreased in cells complemented with a lyase-attenuated Ku mutant. Ku had previously been presumed only to recognize ends and recruit other factors that process ends; our data support an unexpected direct role for Ku in end-processing steps as well.! c/ W4 ]4 u% G' H9 ~
- `* j9 V: w! T/ j+ }海洋注：2楼原文 感谢gaomei210 提供 |
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发表于 2010-4-16 16:20
