4月13日電美國(guó)研究人員最新發(fā)現(xiàn),，一種特殊的蛋白質(zhì)可以有效修復(fù)嚴(yán)重受損的DNA（脫氧核糖核酸）,，這一發(fā)現(xiàn)有望幫助治療因機(jī)體老化、DNA受損而導(dǎo)致的諸多疾病,。
DNA是人類(lèi)主要的遺傳物質(zhì),，染色體由雙鏈DNA分子和組蛋白所組成,。生命科學(xué)研究普遍認(rèn)為,，隨著機(jī)體老化,，染色體內(nèi)DNA會(huì)出現(xiàn)不同程度損傷，這是導(dǎo)致人體出現(xiàn)癌癥以及其他一些與衰老有關(guān)疾病的關(guān)鍵因素,。與此同時(shí)，機(jī)體自身也會(huì)盡力去修復(fù)受損DNA,，但背后具體的機(jī)理人們尚不清楚,。
美國(guó)北卡羅來(lái)納大學(xué)研究人員在最新一期英國(guó)《自然》雜志上發(fā)表報(bào)告說(shuō)，他們研究發(fā)現(xiàn),，一種被稱(chēng)為Ku的蛋白質(zhì)可以通過(guò)特殊方法有效修復(fù)一類(lèi)嚴(yán)重的DNA損傷,。
參與研究的戴爾·拉姆斯登介紹說(shuō)，在各種DNA損傷中,，DNA雙鏈斷裂導(dǎo)致的整個(gè)染色體被破壞,，是最難修復(fù)的一種。這類(lèi)損傷發(fā)生時(shí),，構(gòu)成DNA分子的基本單位——核苷酸可能受到了破壞,。因此，此前科學(xué)家認(rèn)為,，這類(lèi)DNA損傷根本無(wú)法精確修復(fù),。
而他們的最新研究卻發(fā)現(xiàn)，Ku蛋白質(zhì)可以完成這種高難度的修復(fù)工作。它首先定位DNA雙鏈斷裂處,，然后能夠精確地將出問(wèn)題的核苷酸修復(fù),，最后再對(duì)整個(gè)染色體進(jìn)行檢查，“整個(gè)過(guò)程就好比在縫合傷口前首先清洗傷口并為其消毒”,。
研究人員表示,，他們希望在此基礎(chǔ)上能夠獲得更多的有關(guān)DNA損傷修復(fù)的信息，進(jìn)而能夠?qū)ふ业脚c機(jī)體衰老相關(guān)疾病的新療法,。(生物谷Bioon.com)
生物谷推薦原文出處：
Nature doi:10.1038/nature08926
Ku is a 5′-dRP/AP lyase that excises nucleotide damage near broken ends
Steven A. Roberts1, Natasha Strande1, Martin D. Burkhalter1, Christina Strom1, Jody M. Havener1, Paul Hasty2 & Dale A. Ramsden1
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 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
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.
