Mammalian life depends on two distinct pathways of DNA damage tolerance.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36669105.
- Also identified by DOI 10.1073/pnas.2216055120 and PMC identifier 9942833.
- Licence recorded as CC BY-NC-ND.
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Abstract
DNA damage threatens genomic integrity and instigates stem cell failure. To bypass genotoxic lesions during replication, cells employ DNA damage tolerance (DDT), which is regulated via PCNA ubiquitination and REV1. DDT is conserved in all domains of life, yet its relevance in mammals remains unclear. Here, we show that inactivation of both PCNA-ubiquitination and REV1 results in embryonic and adult lethality, and the accumulation of DNA damage in hematopoietic stem and progenitor cells (HSPCs) that ultimately resulted in their depletion. Our results reveal the crucial relevance of DDT in the maintenance of stem cell compartments and mammalian life in unperturbed conditions.
Medical subject headings
- DNA Damage