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The link between 20S proteasome activity and post‐replication DNA repair in Saccharomyces cerevisiae
Author(s) -
Podlaska Agnieszka,
McIntyre Justyna,
Skoneczna Adrianna,
SledziewskaGojska Ewa
Publication year - 2003
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2003.03635.x
Subject(s) - biology , saccharomyces cerevisiae , dna repair , proteasome , gene , genetics , postreplication repair , nucleotide excision repair , dna replication , dna , mutation , dna mismatch repair , dna damage , mutant , phenotype
Summary We have shown previously that deletion of the Saccharomyces cerevisiae UMP1 gene encoding the 20S proteasome maturase causes sensitivity to UV radiation. In the current report, we have extended this finding to show that mutations specifically compromising chymotrypsin‐like or trypsin‐like activity of 20S proteasome peptidases also result in increased UV sensitivity. We have also established that mutations affecting proteasome activity, namely ump1Δ , pre2‐K108R and pup1‐T20A , result in spontaneous and UV‐induced mutator phenotypes. To elucidate the origin of these DNA repair phenotypes of the proteasomal mutants, we performed epistasis analysis, with respect to UV sensitivity, using yeast strains with the UMP1 deletion in different DNA repair backgrounds. We show that UMP1 is not epistatic to RAD23 and RAD2 , which are involved in the nucleotide excision repair (NER) pathway. Instead, our results indicate that UMP1 as well as PUP1 and PRE2 (encoding catalytic subunits of 20S proteasome) belong to an epistatic group of genes functioning in post‐replication DNA repair (PRR) and are hypostatic to RAD18 , which, in complex with RAD6 , plays a central role in PRR. We also show that UMP1 is epistatic to REV3 and RAD30 , although the relationship of UMP1 with these genes is different.