Abstract
Post-replication repair (PRR) allows tolerance of chemical- and UV-induced DNA base lesions in both an error-free and an error-prone manner. In classical PRR, PCNA monoubiquitination recruits translesion synthesis (TLS) DNA polymerases that can replicate through lesions. We find that PRR responds to DNA replication stress that does not cause base lesions. Rad5 forms nuclear foci during normal S phase and after exposure to types of replication stress where DNA base lesions are likely absent. Rad5 binds to the sites of stressed DNA replication forks, where it recruits TLS polymerases to repair single-stranded DNA (ssDNA) gaps, preventing mitotic defects and chromosome breaks. In contrast to the prevailing view of PRR, our data indicate that Rad5 promotes both mutagenic and error-free repair of undamaged ssDNA that arises during physiological and exogenous replication stress.
Keywords:
DNA replication; mutagenesis; post-replication repair; replication stress; single-stranded DNA; translesion synthesis; ubiquitination.
Copyright © 2019 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Chromosomes, Fungal
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DNA Breaks, Single-Stranded*
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DNA Helicases / genetics
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DNA Helicases / metabolism*
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DNA Repair*
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DNA Replication*
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DNA, Fungal / genetics
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DNA, Fungal / metabolism*
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DNA, Single-Stranded / genetics
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DNA, Single-Stranded / metabolism*
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DNA-Directed DNA Polymerase / genetics
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DNA-Directed DNA Polymerase / metabolism
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Mitosis
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Mutation*
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Nucleotidyltransferases / genetics
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Nucleotidyltransferases / metabolism
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Proliferating Cell Nuclear Antigen / genetics
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Proliferating Cell Nuclear Antigen / metabolism
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Protein Binding
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Recombinational DNA Repair
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Saccharomyces cerevisiae / enzymology*
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / growth & development
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
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Ubiquitination
Substances
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DNA, Fungal
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DNA, Single-Stranded
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POL30 protein, S cerevisiae
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Proliferating Cell Nuclear Antigen
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Saccharomyces cerevisiae Proteins
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DNA polymerase zeta
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Nucleotidyltransferases
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REV1 protein, S cerevisiae
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DNA-Directed DNA Polymerase
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RAD5 protein, S cerevisiae
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DNA Helicases