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A gatekeeping function of the replicative polymerase controls pathway choice in the resolution of lesion-stalled replisomes.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 Dec 17; Vol. 116 (51), pp. 25591-25601. Date of Electronic Publication: 2019 Dec 03. - Publication Year :
- 2019
-
Abstract
- DNA lesions stall the replisome and proper resolution of these obstructions is critical for genome stability. Replisomes can directly replicate past a lesion by error-prone translesion synthesis. Alternatively, replisomes can reprime DNA synthesis downstream of the lesion, creating a single-stranded DNA gap that is repaired primarily in an error-free, homology-directed manner. Here we demonstrate how structural changes within the Escherichia coli replisome determine the resolution pathway of lesion-stalled replisomes. This pathway selection is controlled by a dynamic interaction between the proofreading subunit of the replicative polymerase and the processivity clamp, which sets a kinetic barrier to restrict access of translesion synthesis (TLS) polymerases to the primer/template junction. Failure of TLS polymerases to overcome this barrier leads to repriming, which competes kinetically with TLS. Our results demonstrate that independent of its exonuclease activity, the proofreading subunit of the replisome acts as a gatekeeper and influences replication fidelity during the resolution of lesion-stalled replisomes.<br />Competing Interests: The authors declare no competing interest.
- Subjects :
- Escherichia coli genetics
Escherichia coli Proteins chemistry
Escherichia coli Proteins genetics
Escherichia coli Proteins metabolism
DNA Damage genetics
DNA Repair genetics
DNA Replication genetics
DNA, Bacterial chemistry
DNA, Bacterial genetics
DNA, Bacterial metabolism
DNA-Directed DNA Polymerase chemistry
DNA-Directed DNA Polymerase genetics
DNA-Directed DNA Polymerase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 116
- Issue :
- 51
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 31796591
- Full Text :
- https://doi.org/10.1073/pnas.1914485116