Replisome-mediated translesion synthesis by a cellular replicase Journal Article
| Authors: | Nevin, P.; Gabbai, C. C.; Marians, K. J. |
| Article Title: | Replisome-mediated translesion synthesis by a cellular replicase |
| Abstract: | Genome integrity relies on the ability of the replisome to navigate ubiquitous DNA damage during DNA replication. The Escherichia coli replisome transiently stalls at leading-strand template lesions and can either reinitiate replication downstream of the lesion or recruit specialized DNA polymerases that can bypass the lesion via translesion synthesis. Previous results had suggested that the E. coli replicase might play a role in lesion bypass, but this possibility has not been tested in reconstituted DNA replication systems. We report here that the DNA polymerase III holoenzyme in a stalled E. coli replisome can directly bypass a single cyclobutane pyrimidine dimer or abasic site by translesion synthesis in the absence of specialized translesion synthesis polymerases. Bypass efficiency was proportional to deoxynucleotide concentrations equivalent to those found in vivo and was dependent on the frequency of primer synthesis downstream of the lesion. Translesion synthesis came at the expense of lesion-skipping replication restart. Replication of a cyclobutane pyrimidine dimer was accurate, whereas replication of an abasic site resulted in mainly 1 frameshifts. Lesion bypass was accompanied by an increase in base substitution frequency for the base preceding the lesion. These findings suggest that DNA damage at the replication fork can be replicated directly by the replisome without the need to activate error-prone pathways. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc. |
| Keywords: | dna polymerase; dna; escherichia coli; dna replications; replication fork; cyclobutane pyrimidine dimers; polymers; translesion synthesis; aromatic compounds; translesion synthesis polymerase; dna replication system; lesion bypass |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 292 |
| Issue: | 33 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2017-08-18 |
| Start Page: | 13833 |
| End Page: | 13842 |
| Language: | English |
| DOI: | 10.1074/jbc.M117.800441 |
| PROVIDER: | scopus |
| PMCID: | PMC5566535 |
| PUBMED: | 28642369 |
| DOI/URL: | |
| Notes: | Michael Philip Nevin goes by his middle name on the original publication -- Carolina Gabbai's middle initial is incorrect on the original publication -- Article -- Export Date: 2 October 2017 -- Source: Scopus |
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