ORCID

https://orcid.org/• https://orcid.org/0009-0000-3839-2271

Date of Award

2026

Document Type

Dissertation

Degree Name

Biological Sciences (Ph.D.)

Department

Biological Sciences

First Advisor

Ales Vancura

Second Advisor

Ivana Vancurova,

Third Advisor

Yan Zhu

Abstract

My dissertation includes two projects, centered on transcription regulation by checkpoint kinases of the DNA damage response (DDR). The first project focused on the role of checkpoint kinase Mec1p in transcription termination and regulation of the torpedo exonuclease Rat1p. Termination, closely linked with pre-mRNA 3’ processing, dissociates RNA polymerase II (RNAPII) from DNA and releases the nascent RNA transcript. Efficient termination is required for maintaining a pool of RNAPII that is available for re-entry into new transcription cycle. Previous results showed that inactivation of Mec1p in the absence of exogenous genotoxic stress downregulates the efficiency of transcription termination. This study reveals that Mec1p impacts transcription termination at two distinct steps. Mec1p promotes recruitment of Pcf11p, a subunit of the cleavage factor IA (CF IA) to 3’ ends of genes and regulates the activity of torpedo exonuclease Rat1p. Deletion of Mec1p or mutations that prevent activation of Mec1p partially suppress both transcription termination defects as well as rRNA and snoRNA processing defects in rat1-1 cells. These results suggest that the kinase activity of Mec1p downregulates Rat1p function.

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