O-GlcNAc transferase couples MRE11 to transcriptionally active chromatin to suppress DNA damage.

ABSTRACT:

Background

Transcription, metabolism and DNA damage response are tightly regulated to preserve the genomic integrity, and O-GlcNAc transferase (OGT) is positioned to connect the three. Prostate cancer is the most common cancer in men, and androgen-ablation therapy halts disease progression. However, a significant number of prostate cancer patients develop resistance against anti-androgens, and this incurable disease is termed castration-resistant prostate cancer (CRPC). We have shown that combined inhibition of OGT and the transcription elongation kinase CDK9 induce CRPC-selective anti-proliferative effects. Here, we explain the functional basis for these combinatorial effects.

Methods

We used comprehensive mass spectrometry profiling of short-term CDK9 inhibitor effects on

SUBMITTER: Gondane A 

PROVIDER: S-EPMC8842528 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature