Transcriptional mutagenesis dramatically alters genome-wide p53 transactivation landscape.

ABSTRACT: The transcriptional error rate can be significantly increased by the presence of DNA lesions that instruct mis-insertion during transcription; a process referred to as transcriptional mutagenesis (TM) that can result in altered protein function. Herein, we determined the effect of O⁶-methylguanine (O⁶-meG) on transcription and subsequent transactivation activity of p53 in human lung H1299 cells. Levels of TM and effects on transactivation were determined genome wide by RNA-seq. Results showed that 47% of all p53 transcripts contained an uridine misincorporation opposite the lesion at 6 h post transfection, which was decreased to 18% at 24 h. TM at these levels reduced DNA binding activity of p53 to 21% and 80% compared to wild type p53, respectively. Gene expression d

SUBMITTER: Liang S 

PROVIDER: S-EPMC7419513 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature