| Literature DB >> 30773314 |
Jung-Hoon Yoon1, Mark J McArthur2, Jeseong Park1, Debashree Basu1, Maki Wakamiya1, Louise Prakash1, Satya Prakash3.
Abstract
Cancers from sun-exposed skin accumulate "driver" mutations, causally implicated in oncogenesis. Because errors incorporated during translesion synthesis (TLS) opposite UV lesions would generate these mutations, TLS mechanisms are presumed to underlie cancer development. To address the role of TLS in skin cancer formation, we determined which DNA polymerase is responsible for generating UV mutations, analyzed the relative contributions of error-free TLS by Polη and error-prone TLS by Polθ to the replication of UV-damaged DNA and to genome stability, and examined the incidence of UV-induced skin cancers in Polθ-/-, Polη-/-, and Polθ-/- Polη-/- mice. Our findings that the incidence of skin cancers rises in Polθ-/- mice and is further exacerbated in Polθ-/- Polη-/- mice compared with Polη-/- mice support the conclusion that error-prone TLS by Polθ provides a safeguard against tumorigenesis and suggest that cancer formation can ensue in the absence of somatic point mutations.Entities:
Keywords: DNA polymerase η; DNA polymerase θ; UV lesions; UV signature mutations; error-free translesion synthesis; error-prone translesion synthesis; genomic rearrangements; replication stress; replication through UV lesions; skin cancers
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Year: 2019 PMID： 30773314 PMCID： PMC6453116 DOI： 10.1016/j.cell.2019.01.023
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582