一组特定的酶全天监视一个人的DNA,更正DNA复制或损坏导致的复制错误和突变。当这些酶不能正常工作的时候,突变的DNA可能最终导致癌症。尽管科学家报告说这些酶可以修复DNA,科学家还不清楚这些化合物最初究竟如何探测到受损的DNA。
Jacqueline Barton及其同事报告说,这些酶之间发生了长距离的信号传导,把这些化学监视者导向了修复受损DNA的地点。此前的研究提示,这些修复酶在DNA链上下滑动,在根本上感觉这个双螺旋的破损,但是其他报告指出,这类酶太少了,无法让这种监测方法变得可行。这组作者提出,它们的信号传导手段的关键是位于许多这种修复蛋白质内部的一群铁和硫原子,它们可以让DNA链像导线一样连接两个群之间的信号。这组作者证明了干扰这种DNA信号传导的突变阻止了这些酶的通信和触发修复。(生物谷Bioon.com)
生物谷推荐原始出处:
PNAS August 31, 2009, doi: 10.1073/pnas.0908059106
Redox signaling between DNA repair proteins for efficient lesion detection
Amie K. Boala, Joseph C. Genereuxa, Pamela A. Sontza, Jeffrey A. Gralnickb, Dianne K. Newmanc,1 and Jacqueline K. Bartona,1
aDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125;
bDepartment of Microbiology, BioTechnology Institute, University of Minnesota, St. Paul, MN 55108; and
cDepartments of Biology and Earth, Atomospheric and Planetary Science, and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139
Base excision repair (BER) enzymes maintain the integrity of the genome, and in humans, BER mutations are associated with cancer. Given the remarkable sensitivity of DNA-mediated charge transport (CT) to mismatched and damaged base pairs, we have proposed that DNA repair glycosylases (EndoIII and MutY) containing a redox-active [4Fe4S] cluster could use DNA CT in signaling one another to search cooperatively for damage in the genome. Here, we examine this model, where we estimate that electron transfers over a few hundred base pairs are sufficient for rapid interrogation of the full genome. Using atomic force microscopy, we found a redistribution of repair proteins onto DNA strands containing a single base mismatch, consistent with our model for CT scanning. We also demonstrated in Escherichia coli a cooperativity between EndoIII and MutY that is predicted by the CT scanning model. This relationship does not require the enzymatic activity of the glycosylase. Y82A EndoIII, a mutation that renders the protein deficient in DNA-mediated CT, however, inhibits cooperativity between MutY and EndoIII. These results illustrate how repair proteins might efficiently locate DNA lesions and point to a biological role for DNA-mediated CT within the cell.