The homologous recombination protein RAD51D mediates the processing of 6-thioguanine lesions downstream of mismatch repair.

ABSTRACT: Thiopurines are extensively used as immunosuppressants and in the treatment of childhood cancers, even though there is concern about therapy-induced leukemias and myelodysplastic syndromes resulting from thiopurine use. Following metabolic activation, thiopurines are incorporated into DNA and invoke mismatch repair (MMR). Recognition of 6-thioguanine (6-thioG) in DNA by key MMR proteins results in cell death rather than repair. There are suggestions that homologous recombination (HR) is involved downstream of MMR following thiopurine treatment, but the precise role of HR is poorly understood. In this study, we demonstrate that cells deficient in RAD51D (a RAD51 paralogue) are extremely sensitive to 6-thioG. This sensitivity is almost completely rescued by the deletion of Mlh1, which sugges

SUBMITTER: Rajesh P 

PROVIDER: S-EPMC3041871 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature