Our genetic information is subject to constant assault. When unrepaired, DNA lesions could lead to development of deadly diseases such as cancer. Little is known about how machinery in cells that transcribes our genetic material with RNA polymerase II contributes to the integrity of DNA.
We will investigate significance of transcription kinases that are critical for transcription by RNA polymerase II. We already found that one of the kinases, called P-TEFb, is massively activated in response to DNA damage, suggesting that it plays important roles in enabling the genetic integrity. Moreover, another key kinase called Cdk12/CycK, is mutated in many different cancers. We aim to reveal how these mutations misregulate gene transcription and DNA damage repair, contributing to genesis of cancers.
Together, our studies will identify how transcriptional kinase safeguard integrity of DNA. Also, we expect to provide rationale for developing novel therapies against ovarian and other cancers.