Journal
EMBO JOURNAL
Volume 29, Issue 10, Pages 1738-1747Publisher
WILEY
DOI: 10.1038/emboj.2010.64
Keywords
abasic sites; DNA polymerases; DNA repair; DNA replication; translesion synthesis
Categories
Funding
- DFG [SPP 1170]
- Swiss Light Source (SLS)
Ask authors/readers for more resources
Abasic sites represent the most frequent DNA lesions in the genome that have high mutagenic potential and lead to mutations commonly found in human cancers. Although these lesions are devoid of the genetic information, adenine is most efficiently inserted when abasic sites are bypassed by DNA polymerases, a phenomenon termed A-rule. In this study, we present X-ray structures of a DNA polymerase caught while incorporating a nucleotide opposite an abasic site. We found that a functionally important tyrosine side chain directs for nucleotide incorporation rather than DNA. It fills the vacant space of the absent template nucleobase and thereby mimics a pyrimidine nucleobase directing for preferential purine incorporation opposite abasic residues because of enhanced geometric fit to the active site. This amino acid templating mechanism was corroborated by switching to pyrimidine specificity because of mutation of the templating tyrosine into tryptophan. The tyrosine is located in motif B and highly conserved throughout evolution from bacteria to humans indicating a general amino acid templating mechanism for bypass of non-instructive lesions by DNA polymerases at least from this sequence family. The EMBO Journal (2010) 29, 1738-1747. doi: 10.1038/emboj.2010.64; Published online 16 April 2010
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available