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Error-Prone Replication through UV Lesions by DNA Polymerase ? 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 Pol? and error-prone TLS by Pol? to the replication of UV-damaged DNA and to genome stability, and examined the incidence of UV-induced skin cancers in Pol?-/-, Pol?-/-, and Pol?-/- Pol?-/- mice. Our findings that the incidence of skin cancers rises in Pol?-/- mice and is further exacerbated in Pol?-/- Pol?-/- mice compared with Pol?-/- mice support the conclusion that error-prone TLS by Pol? provides a safeguard against tumorigenesis and suggest that cancer formation can ensue in the absence of somatic point mutations.

SUBMITTER: Yoon JH 

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

REPOSITORIES: biostudies-literature

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

Yoon Jung-Hoon JH   McArthur Mark J MJ   Park Jeseong J   Basu Debashree D   Wakamiya Maki M   Prakash Louise L   Prakash Satya S  

Cell 20190214 6

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  ...[more]

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