Nature：修复DNA损伤的关键蛋白质（附原文）

gaomei210

% |8 t  j. H1 F# K" m3 }' K$ U4 l

" |7 P8 ~; x9 x" ]  ?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。) y9 S+ f# j) K5 k8 p, o: q
+ o5 V4 K. m8 {+ q, V, S9 r
DNA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。
1 W) {) z* f/ ?1 }& u$ l1 |3 R4 @1 w8 @2 p7 l0 v
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。
1 X4 n9 a) z0 W: K0 C; ?" {$ h' P3 g8 [" Y5 |
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。
+ Q* v# o) c# p' b
: ^- F  t# N; Z4 x0 W1 |  p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”。# @; a) F) c0 I2 `

1 g. p- _  J1 e/ \; G2 |1 b* d+ n1 M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)
: Y( Z3 D5 q1 u5 P2 B, {5 W5 [$ ^3 o+ d1 y1 |, Y* I- e# c
生物谷推荐原文出处：% d  p; [7 n+ U( L, e- y
) M, u' F* p' m1 u! v7 E
Nature  doi:10.1038/nature08926; V$ X' x0 K/ l* x5 f0 b/ S% u

& b# V5 v# f! lKu is a 5′-dRP/AP lyase that excises nucleotide damage near broken ends
9 P7 `* k9 N- v" Z1 `' XSteven A. Roberts1, Natasha Strande1, Martin D. Burkhalter1, Christina Strom1, Jody M. Havener1, Paul Hasty2 & Dale A. Ramsden1
( ^2 F" \- X7 Q  H; h
3 o/ |# a7 L" E/ a, Z7 y- `1 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
2 a7 |3 c6 W& P4 e. N( \. o2 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 9 R- D7 z( n# W* {8 D5 Q' L
. r% f* A7 k  i0 Q5 C7 O% x
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- f( }5 B1 y

" t0 }/ G0 f" g% ?海洋注：2楼原文 感谢gaomei210 提供

gaomei210

相关文献

冰罗布

谢谢分享

冰罗布

谢谢分享

saberly

xiexie

angel-sakura

谢谢分享，不过衰老的原因是因为这种DNA的严重损伤吗？