期刊
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
卷 643, 期 1-2, 页码 20-28出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.mrfmmm.2008.05.005
关键词
triplex DNA; DNA secondary structure; RecG helicase; RecQ helicase; structure-mediated mutation
资金
- American Heart Association Ohio Valley
- National Institutes of Health [DK061458]
DNA triplex structures can block the replication fork and result in double-stranded DNA breaks (DSBs). RecQ and RecG helicases may be important for replication of such sequences as RecQ resolves synthetic triplex DNA structures and RecG mediates replication restart by fork regression. Primer extension on an 88bp triplex-forming polypurine center dot polypyrimicline (Pu center dot Py) tract from the PKD1 gene demonstrated that RecQ, but not RecG, facilitated primer extension by T7 DNA polymerase. A high-throughput, dual plasmid screening system using isogenic bacterial lines deficient in RecG, RecQ, or both, revealed that RecQ deficiency increased mutation to sequence flanking this 88 bp tract by eight to ten-fold. Although RecG facilitated small deletions in an 88 bp mirror repeat-containing sequence, it was absolutely required to maintain a 2.5 kb Pu center dot Py tract containing multiple mirror repeats. These results support a two-tiered model where RecQ facilitates fork progression through triplex-forming tracts and, failing processivity, RecG is critical for replication fork restart. (c) 2008 Elsevier B.V. All rights reserved.
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