Error-free DNA damage tolerance and sister chromatid proximity during DNA replication rely on the Polα/Primase/Ctf4 Complex

Chromosomal replication is entwined with DNA damage tolerance (DDT) and chromatin structure establishment via elusive mechanisms. Here we examined how specific replication conditions affecting replisome architecture and repriming impact on DDT. We show that Saccharomyces cerevisiae Polα/Primase/Ctf4...

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Vydáno v:Molecular cell Ročník 57; číslo 5; s. 812
Hlavní autoři: Fumasoni, Marco, Zwicky, Katharina, Vanoli, Fabio, Lopes, Massimo, Branzei, Dana
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 05.03.2015
Témata:
Chromatids - genetics
DNA Damage
DNA Polymerase I - genetics
DNA Polymerase I - metabolism
DNA Primase - genetics
DNA Primase - metabolism
DNA Repair - genetics
DNA Replication - genetics
DNA, Single-Stranded - genetics
DNA, Single-Stranded - metabolism
DNA, Single-Stranded - ultrastructure
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
G2 Phase Cell Cycle Checkpoints - genetics
Microscopy, Electron
Models, Genetic
Multiprotein Complexes - genetics
Multiprotein Complexes - metabolism
Mutation
Recombination, Genetic
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Signal Transduction - genetics
Time Factors
ISSN:1097-4164, 1097-4164
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Shrnutí:Chromosomal replication is entwined with DNA damage tolerance (DDT) and chromatin structure establishment via elusive mechanisms. Here we examined how specific replication conditions affecting replisome architecture and repriming impact on DDT. We show that Saccharomyces cerevisiae Polα/Primase/Ctf4 mutants, proficient in bulk DNA replication, are defective in recombination-mediated damage-bypass by template switching (TS) and have reduced sister chromatid cohesion. The decrease in error-free DDT is accompanied by increased usage of mutagenic DDT, fork reversal, and higher rates of genome rearrangements mediated by faulty strand annealing. Notably, the DDT defects of Polα/Primase/Ctf4 mutants are not the consequence of increased sister chromatid distance, but are instead caused by altered single-stranded DNA metabolism and abnormal replication fork topology. We propose that error-free TS is driven by timely replicative helicase-coupled re-priming. Defects in this event impact on replication fork architecture and sister chromatid proximity, and represent a frequent source of chromosome lesions upon replication dysfunctions.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1097-4164
1097-4164
DOI:10.1016/j.molcel.2014.12.038