Journal article
Coordinated degradation of replisome components ensures genome stability upon replication stress in the absence of the replication fork protection complex
PLoS genetics, v 9(1), pp e1003213-e1003213
2013
PMID: 23349636
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The stabilization of the replisome complex is essential in order to achieve highly processive DNA replication and preserve genomic integrity. Conversely, it would also be advantageous for the cell to abrogate replisome functions to prevent inappropriate replication when fork progression is adversely perturbed. However, such mechanisms remain elusive. Here we report that replicative DNA polymerases and helicases, the major components of the replisome, are degraded in concert in the absence of Swi1, a subunit of the replication fork protection complex. In sharp contrast, ORC and PCNA, which are also required for DNA replication, were stably maintained. We demonstrate that this degradation of DNA polymerases and helicases is dependent on the ubiquitin-proteasome system, in which the SCF(Pof3) ubiquitin ligase is involved. Consistently, we show that Pof3 interacts with DNA polymerase ε. Remarkably, forced accumulation of replisome components leads to abnormal DNA replication and mitotic catastrophes in the absence of Swi1. Swi1 is known to prevent fork collapse at natural replication block sites throughout the genome. Therefore, our results suggest that the cell elicits a program to degrade replisomes upon replication stress in the absence of Swi1. We also suggest that this program prevents inappropriate duplication of the genome, which in turn contributes to the preservation of genomic integrity.
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Details
- Title
- Coordinated degradation of replisome components ensures genome stability upon replication stress in the absence of the replication fork protection complex
- Creators
- Laura C Roseaulin - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USAChiaki NoguchiEsteban MartinezMelissa A ZieglerTakashi TodaEishi Noguchi
- Publication Details
- PLoS genetics, v 9(1), pp e1003213-e1003213
- Publisher
- Public LIbrary of Science (PLOS); United States
- Grant note
- GM077604 / NIGMS NIH HHS Cancer Research UK R01 GM077604 / NIGMS NIH HHS R01GM077604-S1 / NIGMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000314651500055
- Scopus ID
- 2-s2.0-84873495712
- Other Identifier
- 991014877882004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Genetics & Heredity