來自華盛頓州立大學(xué)的研究人員發(fā)現(xiàn)了一種方法能使癌細(xì)胞正常老化和死亡，這有望開辟新穎的減緩,，甚至停止腫瘤生長(zhǎng)的方式,。
"如果可能的話，我們能夠使癌細(xì)胞像正常細(xì)胞那樣死亡,，"華盛頓州立大學(xué)分子生物學(xué)學(xué)院的副教授Weihang Chai表示,，"大體上可使癌細(xì)胞在"永生"中受到威脅。"
我們知道,，正常細(xì)胞每次在復(fù)制的時(shí)候會(huì)丟失一些他們?cè)鹊腄NA,，即DNA分子鏈的保護(hù)端-端粒的部分丟失。最終的結(jié)果是,，端粒變得太短,，發(fā)出使細(xì)胞停止復(fù)制和生長(zhǎng)的信號(hào)。
癌細(xì)胞具有保持DNA鏈縮減的機(jī)制,，這使得它們具有幾乎永恒的生命,。這是因?yàn)槎肆Ｃ笖U(kuò)展了癌細(xì)胞的DNA,，而其他的蛋白促使了另一條鏈的延伸。
Chai和她的同事們,，在最新一期的EMBO Journal雜志上發(fā)布了這項(xiàng)研究,，他們發(fā)現(xiàn)一個(gè)調(diào)控蛋白能夠控制第二股鏈的延伸，另外還發(fā)現(xiàn)了一種對(duì)該鏈合成來說是必需的蛋白,。
Chai表示,，如果第二股DNA鏈不能被延長(zhǎng)，那么癌細(xì)胞就會(huì)像正常細(xì)胞那樣運(yùn)作,，像正常細(xì)胞那樣死亡,。研究團(tuán)隊(duì)目前正關(guān)注于抑制這種調(diào)控蛋白發(fā)揮功能的策略開發(fā)。(生物谷Bioon.com)
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生物谷推薦原文出處：
The EMBO Journal doi:10.1038/emboj.2010.156
Molecular steps of G-overhang generation at human telomeres and its function in chromosome end protection
Xueyu Dai1,2,4, Chenhui Huang1,2,4, Amruta Bhusari3,4,5, Shilpa Sampathi1,2, Kathryn Schubert1 and Weihang Chai1,2
1 WWAMI Medical Education Program, Washington State University, Spokane, WA, USA
2 School of Molecular Biosciences, Washington State University, Pullman, WA, USA
3 Department of Biology, Texas Woman's University, Denton, TX, USA
Telomeric G-overhangs are required for the formation of the protective telomere structure and telomerase action. However, the mechanism controlling G-overhang generation at human telomeres is poorly understood. Here, we show that G-overhangs can undergo cell cycle-regulated changes independent of telomerase activity. G-overhangs at lagging telomeres are lengthened in S phase and then shortened in late S/G2 because of C-strand fill-in, whereas the sizes of G-overhangs at leading telomeres remain stable throughout S phase and are lengthened in G2/M. The final nucleotides at measurable C-strands are precisely defined throughout the cell cycle, indicating that C-strand resection is strictly regulated. We demonstrate that C-strand fill-in is mediated by DNA polymerase α (polα) and controlled by cyclin-dependent kinase 1 (CDK1). Inhibition of CDK1 leads to accumulation of lengthened G-overhangs and induces telomeric DNA damage response. Furthermore, depletion of hStn1 results in elongation of G-overhangs and an increase in telomeric DNA damage. Our results suggest that G-overhang generation at human telomeres is regulated by multiple tightly controlled processes and C-strand fill-in is under the control of polα and CDK1.
