加州大学戴维斯分校的科学家发现,一种在DNA拷贝方面起关键作用的蛋白同样在修复裂口方面具有重要作用。这项研究有助于科学家理解癌细胞抑制辐射和化疗的机制,同样有助于理解细胞如何在一开始发生癌变。
一种能激增细胞核抗原的蛋白会形成了一个环,装配在DNA双螺旋结构周围。该环有助于固定DNA聚合酶。DNA聚合酶使得细胞在分裂成两个新的细胞时能够形成一个DNA链的拷贝。
这项研究结果发布在11月25日的Molecular Cell上,表明在DNA重组中,增殖细胞核抗原(PCNA)能执行相似的功能。
研究人员开发了一个系统,他们使用设计的DNA底物和纯化蛋白,在试管中检测一些其他分子的行为,这些分子同时包含在DNA拷贝和DNA修复中。
Heyer的实验室开始是使用酵母进行实验的,但是酵母不能获得癌症。但研究人员注意到,酵母的DNA重组和修复机制和人类基本上是相同的。
放疗和癌症药物同样会使癌细胞DNA发生缺口,过多的缺口可以使致命细胞死亡。但是细胞修复装置会修复裂口。
理解DNA重组和修复的机制,为癌症治疗开辟了一条新的道路,使肿瘤更易于治疗,或者预测病人对特定疗法的效果。这项研究同样表明,基因使得有些人更易受到癌症影响。比如,“乳腺癌基因”BRCA-2,该基因参与DNA修复。(生物谷Bioon.com)
生物谷推荐原始出处:
Molecular Cell, Volume 36, Issue 4, 704-713, 25 November 2009 doi:10.1016/j.molcel.2009.09.036
PCNA Is Required for Initiation of Recombination-Associated DNA Synthesis by DNA Polymerase δ
Xuan Li1, 4, Carrie M. Stith3, Peter M. Burgers3 and Wolf-Dietrich Heyer1, 2, ,
1 Department of Microbiology, University of California, Davis, Davis, CA 95616-8665, USA
2 Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616-8665, USA
3 Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA
Genetic recombination ensures proper chromosome segregation during meiosis and is essential for genome stability and tumor suppression. DNA synthesis after Rad51-mediated DNA strand invasion is a crucial step during recombination. PCNA is known as the processivity clamp for DNA polymerases. Here, we report the surprising observation that PCNA is specifically required to initiate recombination-associated DNA synthesis in the extension of the 3′ end of the invading strand in a D loop. We show using a reconstituted system of yeast Rad51, Rad54, RPA, PCNA, RFC, and DNA polymerase δ that loading of PCNA by RFC targets DNA polymerase δ to the D loop formed by Rad51 protein, allowing efficient utilization of the invading 3′ end and processive DNA synthesis. We conclude that PCNA has a specific role in the initiation of recombination-associated DNA synthesis and that DNA polymerase δ promotes recombination-associated DNA synthesis.