Journal
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
Volume 478, Issue 1-2, Pages 129-139Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0027-5107(01)00131-2
Keywords
polymerase eta; spontaneous mutagenesis; mismatch repair; exonucleolytic proofreading; replication fidelity
Ask authors/readers for more resources
DNA polymerase eta synthesizes DNA in vitro with low fidelity. Based on this, here we report the effects of deletion or increased expression of yeast RAD30 gene, encoding for polymerase eta (Pol eta), on spontaneous mutagenesis in vivo. Deletion of RAD30 did not affect spontaneous mutagenesis. Overproduction of Rad30p was slightly mutagenic in a wild-type yeast strain and moderately mutagenic in strains with inactive 3 ' --> 5 ' -exonuclease of DNA polymerase epsilon or DNA mismatch repair. These data suggest that excess Rad30p reduces replication fidelity in vivo and that the induced errors may be corrected by exonucleolytic proofreading and DNA mismatch repair. However, the magnitude of mutator effect (only up to 10-fold) suggests that the replication fork is protected from inaccurate synthesis by Pol eta in the absence of DNA damage. Overproduction of catalytically inactive Rad30p was also mutagenic, suggesting that much of the mutator effect results from indirect perturbation of replication rather than from direct misincorporation by Po eta. Moreover, while excess wild-type Pol eta primarily induced base substitutions in the msh6 and pms1 strains, excess inactive Rad30p induced both base substitutions and frameshifts. This suggests that more than one mutagenic mechanism is operating when RAD30 is overexpressed. Published by Elsevier Science B.V.
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