Ubx5-Cdc48 assists the protease Wss1 at DNA-protein crosslink sites in yeast.

ABSTRACT: DNA-protein crosslinks (DPCs) pose a serious threat to genome stability. The yeast proteases Wss1, 26S proteasome, and Ddi1 are safeguards of genome integrity by acting on a plethora of DNA-bound proteins in different cellular contexts. The AAA ATPase Cdc48/p97 is known to assist Wss1/SPRTN in clearing DNA-bound complexes; however, its contribution to DPC proteolysis remains unclear. Here, we show that the Cdc48 adaptor Ubx5 is detrimental in yeast mutants defective in DPC processing. Using an inducible site-specific crosslink, we show that Ubx5 accumulates at persistent DPC lesions in the absence of Wss1, which prevents their efficient removal from the DNA. Abolishing Cdc48 binding or complete loss of Ubx5 suppresses sensitivity of wss1∆ cells to DPC-inducing agents by favoring alternate

SUBMITTER: Noireterre A 

PROVIDER: S-EPMC10308373 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature