Error-Prone Replication through UV Lesions by DNA Polymerase θ Protects against Skin Cancers.

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 exa

SUBMITTER: Yoon JH 

PROVIDER: S-EPMC6453116 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature