Journal
MOLECULAR CELL
Volume 49, Issue 5, Pages 1010-1015Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2012.12.021
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Funding
- Division of Intramural Research of the National Institutes of Health, National Institute of Environmental Health Sciences [Z01 ES065070]
- Swedish Foundation for Strategic Research
- Swedish Research Council
- Swedish Cancer Society
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RNase H2-dependent ribonucleotide excision repair (RER) removes ribonucleotides incorporated during DNA replication. When RER is defective, ribonucleotides in the nascent leading strand of the yeast genome are associated with replication stress and genome instability. Here, we provide evidence that topoisomerase 1 (Top1) initiates an independent form of repair to remove ribonucleotides from genomic DNA. This Top1-dependent process activates the S phase checkpoint. Deleting TOP1 reverses this checkpoint activation and also relieves replication stress and genome instability in RER-defective cells. The results reveal an additional removal pathway for a very common lesion in DNA, and they imply that the dirty DNA ends created when Top1 incises ribonucleotides in DNA are responsible for the adverse consequences of ribonucleotides in RNase H2-defective cells.
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