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Identifying Deubiquitinase Regulating the DNA Damage Response Pathway
Author(s) -
Cranley Juliana,
Baker James,
Pauer Emma,
Cheranda Nina,
Weng Fangli,
Wang Yuqi
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.0r410
Subject(s) - deubiquitinating enzyme , dna damage , g2 m dna damage checkpoint , ubiquitin , checkpoint kinase 2 , chek1 , microbiology and biotechnology , dna repair , cell cycle checkpoint , mutant , chemistry , dna , biology , protein kinase a , biochemistry , kinase , cell cycle , cell , gene , protein serine threonine kinases
In response to DNA damage, cells often activate Mec1‐dependent DNA damage checkpoint, resulting in the activation of the effector kinase Rad53 that promotes cell cycle arrest and DNA repair. The checkpoint proteins and the DNA damage response pathway are often regulated by ubiquitination, a reversible post‐translational modification, raising the possibility that checkpoint activation may be regulated by a deubiquitinating enzyme. To test this, we screened a collection of yeast deubiquitinating enzyme deletion mutants and monitored their responses to DNA damage agents. Interestingly, we find that one deubiquitinating enzyme deletion mutant displayed consistently decreased levels of checkpoint activation. Further analysis indicated that this mutant does not affect either the abundance or the stability of checkpoint activators, but it rather has a profound effect on Mec1 itself. This analysis suggests deubiquitinating enzyme as a novel regulator for Mecl1 and DNA damage checkpoint pathway.