DNA Polymerase Beta Germline Variant Confers Cellular Response to Cisplatin Therapy.

ABSTRACT: Resistance to cancer chemotherapies leads to deadly consequences, yet current research focuses only on the roles of somatically acquired mutations in this resistance. The mutational status of the germline is also likely to play a role in the way cells respond to chemotherapy. The carrier status for the POLB rs3136797 germline mutation encoding P242R DNA polymerase beta (Pol β) is associated with poor prognosis for lung cancer, specifically in response to treatment with cisplatin. Here, it is revealed that the P242R mutation is sufficient to promote resistance to cisplatin in human cells and in mouse xenografts. Mechanistically, P242R Pol β acts as a translesion polymerase and prefers to insert the correct nucleotide opposite cisplatin intrastrand cross-links, leading to the activati

SUBMITTER: Nemec AA 

PROVIDER: S-EPMC5334281 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature