CDK12 regulates DNA repair genes by suppressing intronic polyadenylation.

ABSTRACT: Mutations that attenuate homologous recombination (HR)-mediated repair promote tumorigenesis and sensitize cells to chemotherapeutics that cause replication fork collapse, a phenotype known as 'BRCAness'¹. BRCAness tumours arise from loss-of-function mutations in 22 genes¹. Of these genes, all but one (CDK12) function directly in the HR repair pathway¹. CDK12 phosphorylates serine 2 of the RNA polymerase II C-terminal domain heptapeptide repeat^2-7, a modification that regulates transcription elongation, splicing, and cleavage and polyadenylation^8,9. Genome-wide expression studies suggest that depletion of CDK12 abrogates the expression of several HR genes relatively specifically, thereby blunting HR repair^3-7,10,11. This obs

SUBMITTER: Dubbury SJ 

PROVIDER: S-EPMC6328294 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature