Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37058556.
- Also identified by DOI 10.1126/sciadv.ade7997 and PMC identifier 10104471.
- Licence recorded as CC BY-NC.
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Abstract
Recent studies have described a DNA damage tolerance pathway choice that involves a competition between PrimPol-mediated repriming and fork reversal. Screening different translesion DNA synthesis (TLS) polymerases by the use of tools for their depletion, we identified a unique role of Pol ι in regulating such a pathway choice. Pol ι deficiency unleashes PrimPol-dependent repriming, which accelerates DNA replication in a pathway that is epistatic with ZRANB3 knockdown. In Pol ι-depleted cells, the excess participation of PrimPol in nascent DNA elongation reduces replication stress signals, but thereby also checkpoint activation in S phase, triggering chromosome instability in M phase. This TLS-independent function of Pol ι requires its PCNA-interacting but not its polymerase domain. Our findings unravel an unanticipated role of Pol ι in protecting the genome stability of cells from detrimental changes in DNA replication dynamics caused by PrimPol.
Medical subject headings
- DNA-Directed DNA Polymerase
- DNA Replication