Evidence that processing of ribonucleotides in DNA by topoisomerase 1 is leading-strand specific
| Autor: | Scott A. Lujan, Anders R. Clausen, Lisette Marjavaara, Thomas A. Kunkel, Andrei Chabes, Alan B. Clark, Peter M. J. Burgers, Jessica S. Williams |
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| Rok vydání: | 2015 |
| Předmět: |
DNA Replication
Saccharomyces cerevisiae Proteins Ribonucleotide DNA clamp DNA Repair biology Chemistry DNA polymerase Ribonucleotide excision repair DNA polymerase II DNA replication DNA DNA Polymerase II Saccharomyces cerevisiae Ribonucleotides Molecular biology DNA polymerase delta Article DNA Topoisomerases Type I Structural Biology Prokaryotic DNA replication biology.protein Molecular Biology |
| Zdroj: | Nature Structural & Molecular Biology. 22:291-297 |
| ISSN: | 1545-9985 1545-9993 |
| DOI: | 10.1038/nsmb.2989 |
| Popis: | Ribonucleotides incorporated during nuclear DNA replication are removed by RNase H2-dependent ribonucleotide excision repair (RER). When RER is defective, topoisomerase 1 (Top1) incises the DNA at unrepaired ribonucleotides, initiating their removal but accompanied by slow growth, replicative stress and a strongly increased rate of short deletions. Here we show that these phenotypes are incurred by a high level of ribonucleotides incorporated by a variant of the major leading strand replicase, DNA polymerase ε (Pol ε), but not by orthologous variants of the lagging strand replicases, Pols α or δ. Moreover, in the absence of RER, increased ribonucleotide incorporation by Pol ε, but not by Pols α or δ, is lethal in combination with loss of RNase H1. Several explanations for this asymmetry are considered, including the idea that Top1 incision at ribonucleotides relieves torsional stress in the nascent leading strand but not in the discontinuous nascent lagging strand, where preexisting nicks prevent the accumulation of superhelical tension. |
| Databáze: | OpenAIRE |
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