Coordination between nucleotide excision repair and specialized polymerase DnaE2 action enables DNA damage survival in non-replicating bacteria
- National Centre for Biological Sciences, India
Abstract
Translesion synthesis (TLS) is a highly conserved mutagenic DNA lesion tolerance pathway, which employs specialized, low-fidelity DNA polymerases to synthesize across lesions. Current models suggest that activity of these polymerases is predominantly associated with ongoing replication, functioning either at or behind the replication fork. Here we provide evidence for DNA damage-dependent function of a specialized polymerase, DnaE2, in replication-independent conditions. We develop an assay to follow lesion repair in non-replicating Caulobacter and observe that components of the replication machinery localize on DNA in response to damage. These localizations persist in the absence of DnaE2 or if catalytic activity of this polymerase is mutated. Single-stranded DNA gaps for SSB binding and low-fidelity polymerase-mediated synthesis are generated by nucleotide excision repair, as replisome components fail to localize in the absence of NER. This mechanism of gap-filling facilitates cell cycle restoration when cells are released into replication-permissive conditions. Thus, such cross-talk (between activity of NER and specialized polymerases in subsequent gap-filling) helps preserve genome integrity and enhances survival in a replication-independent manner.
Data availability
Data analysed during this study are included in the manuscript. Numerical data files (source data files) have been provided for Figure 1_figure supplement1, Figure 2-5 and corresponding figure supplements.
Article and author information
Author details
Anjana Badrinarayanan
Funding
Human Frontier of Sciences Programme (00051/ 2017-C)
- Anjana Badrinarayanan
Department of Atomic Energy, Government of India (12-R&D-TFR-5.04-0800)
- Anjana Badrinarayanan
Department of Science and Technology, Ministry of Science and Technology, India (PDF/2018/001164)
- Asha Mary Joseph
Department of Biotechnology, Ministry of Science and Technology, India (IYBA)
- Anjana Badrinarayanan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Joseph et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Coordination between nucleotide excision repair and specialized polymerase DnaE2 action enables DNA damage survival in non-replicating bacteria
eLife 10:e67552.
https://doi.org/10.7554/eLife.67552
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