Delayed DNA joining at 3' mismatches by human DNA ligases
Open Access
- 15 October 1999
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 27 (20) , 4028-4033
- https://doi.org/10.1093/nar/27.20.4028
Abstract
Repair synthesis catalysed by DNA polymerase β at 1 nt gaps occurs in the main pathway of mammalian base excision repair. DNA polymerase β has no exonucleolytic proof-reading ability, and exhibits high error frequency during DNA synthesis. Consequently, continuous correction of endogenous DNA damage by short-patch repair synthesis might lead to a high spontaneous mutation rate, unless subsequent steps in the repair pathway allow for selective removal of incorporation errors. We show here that both human DNA ligase I and III discriminate strongly between a correctly paired versus a mispaired residue at the 3′ position of a nick in DNA, when assayed in the presence of physiological concentrations of KCI. The resulting delay in joining after misincorporation by DNA polymerase β during gap filling could allow for removal of the mismatched terminal residue by a distinct 3′ exonuclease.Keywords
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