High-resolution genomic assays provide insight into the division of labor between TLS and HDR in mammalian replication of damaged DNA.

摘要: The multitude of DNA lesions that continuously form in cannot all be detected and removed prior to replication. Thus, encounters the replication fork with damage become inevitable. Such inhibit progression, leading arrest or re-priming downstream site. Either these events will result formation gap-lesion structures, which a damaged base is located single stranded stretch DNA, vulnerable subsequent nicking. double strand break would ensue if ssDNA becomes nicked constitutes escalation from nucleotide(s)-specific chromosomal scale. Cells employ two universal tolerance (DDT) strategies resolve situations, by converting structures into dsDNA without repairing damage. first translesion synthesis (TLS), specialized low-fidelity polymerase inserts nucleotide opposite one. TLS inherently mutagenic, due miscoding nature most nucleotides. second strategy homology-dependent repair (HDR), relies on presence an identical intact sister chromatid. molecular mechanisms regulate division labor between pathways are poorly understood. This review focuses balance HDR mammalian cells, discussing recent findings were made possible thanks newly developed high resolution genomic assays, highlighting role lesion's properties DDT pathway choice.