A regulatory phosphorylation site on Mec1 controls chromatin occupancy of RNA polymerases during replication stress.

ABSTRACT: Upon replication stress, budding yeast checkpoint kinase Mec1^ATR triggers the downregulation of transcription, thereby reducing the level of RNA polymerase (RNAP) on chromatin to facilitate replication fork progression. Here, we identify a hydroxyurea-induced phosphorylation site on Mec1, Mec1-S1991, that contributes to the eviction of RNAPII and RNAPIII during replication stress. The expression of the non-phosphorylatable mec1-S1991A mutant reduces replication fork progression genome-wide and compromises survival on hydroxyurea. This defect can be suppressed by destabilizing chromatin-bound RNAPII through a TAP fusion to its Rpb3 subunit, suggesting that lethality in mec1-S1991A mutants arises from replication-transcription conflicts. Coincident with a failure to repress gene e

SUBMITTER: Hurst V 

PROVIDER: S-EPMC8561635 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature