一組特定的酶全天監(jiān)視一個人的DNA,，更正DNA復(fù)制或損壞導(dǎo)致的復(fù)制錯誤和突變。當(dāng)這些酶不能正常工作的時候,，突變的DNA可能最終導(dǎo)致癌癥,。盡管科學(xué)家報告說這些酶可以修復(fù)DNA，科學(xué)家還不清楚這些化合物最初究竟如何探測到受損的DNA,。
Jacqueline Barton及其同事報告說,，這些酶之間發(fā)生了長距離的信號傳導(dǎo)，把這些化學(xué)監(jiān)視者導(dǎo)向了修復(fù)受損DNA的地點(diǎn)。此前的研究提示,，這些修復(fù)酶在DNA鏈上下滑動,，在根本上感覺這個雙螺旋的破損，但是其他報告指出,，這類酶太少了,，無法讓這種監(jiān)測方法變得可行。這組作者提出,，它們的信號傳導(dǎo)手段的關(guān)鍵是位于許多這種修復(fù)蛋白質(zhì)內(nèi)部的一群鐵和硫原子，它們可以讓DNA鏈像導(dǎo)線一樣連接兩個群之間的信號,。這組作者證明了干擾這種DNA信號傳導(dǎo)的突變阻止了這些酶的通信和觸發(fā)修復(fù),。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
