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Primase excites the competition of templating transcription and lagging replication to boost DNA damage

ABSTRACT: Head-on transcription-replication conflicts (HO-TRCs) cause R-loops and DNA damage. We realized that HO-TRCs are the natural competition for templating transcription and lagging replication in the same DNA strand (termed TemLag competition), however, the regulatory mechanisms behind are unclear. We previously identified a chloroplast-localized RNase H1 protein AtRNH1C that can remove R-loops and relax HO-TRCs for genome integrity. Through the mutagenesis screen, we identified that the chloroplast-localized primase ATH exacerbates TemLag competition in the atrnh1c mutant. A mutation in ATH weakens the binding affinity of DNA, thus slowing down DNA replication and relieving TemLag competition. Overexpression of ATH boosts TemLag competition and intensifies DNA damage. Interestingly, strand-specific DNA damage sequencing reveals that TemLag competition induces single-strand DNA damage of the competitive strand at the end of transcription. These results illustrated a potentially conserved mechanism among organisms, of which the primase antagonizes R-loop clearance machinery to exaggerate TemLag competition and genome instability.

ORGANISM(S): Arabidopsis thaliana

PROVIDER: GSE215443 | GEO | 2023/12/06

REPOSITORIES: GEO

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