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Temporal Regulation of Head-on Transcription at Replication Initiation Sites

ABSTRACT: Head-on collisions between the DNA replication machinery and RNA polymerase are potent genotoxic events leading to replication fork stalling, R-loop formation, and DNA breaks. Current models suggest that head-on collisions are avoided through replication initiation site (RIS) placement upstream of active genes, thus ensuring co-orientation of replication fork movement and genic transcription. However, this model does not account for pervasive transcription units, or intragenic replication initiation events. Through mining phased GRO-seq data, and developing a rigorous informatic strategy to identify RIS, we demonstrate that head-on transcription occurs frequently in a breast cancer cell line, and that this transcription is significantly downregulated during S-phase, particularly in regions susceptible to R-loop formation. Collectively, our analysis suggests the existence of a temporally tuned transcriptional regulation mechanism that functions to maintain genome stability.

ORGANISM(S): Homo sapiens

PROVIDER: GSE201746 | GEO | 2022/04/30

REPOSITORIES: GEO

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