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Plos Biology : an Aromatic Sensor with Aversion to Damaged Strands Confers Versatility to Dna Repair, Volume 5

By Tainer, John

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Book Id: WPLBN0003926894
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos Biology : an Aromatic Sensor with Aversion to Damaged Strands Confers Versatility to Dna Repair, Volume 5  
Author: Tainer, John
Volume: Volume 5
Language: English
Subject: Journals, Science, Biology
Collections: Periodicals: Journal and Magazine Collection (Contemporary), PLoS Biology
Historic
Publication Date:
Publisher: Plos

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Tainer, J. (n.d.). Plos Biology : an Aromatic Sensor with Aversion to Damaged Strands Confers Versatility to Dna Repair, Volume 5. Retrieved from http://hawaiilibrary.net/


Description
Description : It was not known how xeroderma pigmentosum group C (XPC) protein, the primary initiator of global nucleotide excision repair, achieves its outstanding substrate versatility. Here, we analyzed the molecular pathology of a unique Trp690Ser substitution, which is the only reported missense mutation in xeroderma patients mapping to the evolutionary conserved region of XPC protein. The function of this critical residue and neighboring conserved aromatics was tested by site-directed mutagenesis followed by screening for excision activity and DNA binding. This comparison demonstrated that Trp690 and Phe733 drive the preferential recruitment of XPC protein to repair substrates by mediating an exquisite affinity for single-stranded sites. Such a dual deployment of aromatic side chains is the distinctive feature of functional oligonucleotide/oligosaccharide-binding folds and, indeed, sequence homologies with replication protein A and breast cancer susceptibility 2 protein indicate that XPC displays a monomeric variant of this recurrent interaction motif. An aversion to associate with damaged oligonucleotides implies that XPC protein avoids direct contacts with base adducts. These results reveal for the first time, to our knowledge, an entirely inverted mechanism of substrate recognition that relies on the detection of single-stranded configurations in the undamaged complementary sequence of the double helix.

 

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