Affiliation:
1. Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555-1061
Abstract
ABSTRACT
UV lesions in the template strand block the DNA replication machinery. Genetic studies of the yeast
Saccharomyces cerevisiae
have indicated the requirement of the Rad6-Rad18 complex, which contains ubiquitin-conjugating and DNA-binding activities, in the error-free and mutagenic modes of damage bypass. Here, we examine the contributions of the
REV3
,
RAD30
,
RAD5
, and
MMS2
genes, all of which belong to the
RAD6
epistasis group, to the postreplication repair of UV-damaged DNA. Discontinuities, which are formed in DNA strands synthesized from UV-damaged templates, are not repaired in the
rad5Δ
and
mms2Δ
mutants, thus indicating the requirement of the Rad5 protein and the Mms2-Ubc13 ubiquitin-conjugating enzyme complex in this repair process. Some discontinuities accumulate in the absence of
RAD30
-encoded DNA polymerase η (Polη) but not in the absence of
REV3
-encoded DNA Polζ. We concluded that replication through UV lesions in yeast is mediated by at least three separate Rad6-Rad18-dependent pathways, which include mutagenic translesion synthesis by Polζ, error-free translesion synthesis by Polη, and postreplication repair of discontinuities by a Rad5-dependent pathway. We suggest that newly synthesized DNA possessing discontinuities is restored to full size by a “copy choice” type of DNA synthesis which requires Rad5, a DNA-dependent ATPase, and also PCNA and Polδ. The possible roles of the Rad6-Rad18 and the Mms2-Ubc13 enzyme complexes in Rad5-dependent damage bypass are discussed.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
159 articles.
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