TLP-mediated global transcriptional repression after double-strand DNA breaks slows down DNA repair and induces apoptosis.

ABSTRACT: Transcription and DNA damage repair act in a coordinated manner. Recent studies have shown that double-strand DNA breaks (DSBs) are repaired in a transcription-coupled manner. Active transcription results in a faster recruitment of DSB repair factors and expedites DNA repair. On the other hand, transcription is repressed by DNA damage through multiple mechanisms. We previously reported that TLP, a TATA box-binding protein (TBP) family member that functions as a transcriptional regulator, is also involved in DNA damage-induced apoptosis. However, the mechanism by which TLP affects DNA damage response was largely unknown. Here we show that TLP-mediated global transcriptional repression after DSBs is crucial for apoptosis induction by DNA-damaging agents such as etoposide and doxorubicin. Com

SUBMITTER: Suzuki H 

PROVIDER: S-EPMC6425004 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature