Send to:

Choose Destination
See comment in PubMed Commons below
Mutat Res. 2006 Jan 29;593(1-2):153-63. Epub 2005 Aug 10.

Analysis of the spontaneous mutator phenotype associated with 20S proteasome deficiency in S. cerevisiae.

Author information

  • 1Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland.


Besides its role as a major recycler of unfolded or otherwise damaged intracellular proteins, the 26S proteasome functions as a regulator of many vital cellular processes and is postulated as a target for antitumor drugs. It has previously been shown that dysfunction of the catalytic core of the 26S proteasome, the 20S proteasome, causes a moderate increase in the frequency of spontaneous mutations in yeast [A. Podlaska, J. McIntyre, A. Skoneczna, E. Sledziewska-Gojska, The link between proteasome activity and postreplication DNA repair in Saccharomyces cerevisiae. Mol. Microbiol. 49 (2003) 1321-1332]. Here we show the results of genetic analysis, which indicate that the mutator phenotype caused by the deletion of UMP1, encoding maturase of 20S proteasome, involves members of the RAD6 epistasis group. The great majority of mutations occurring spontaneously in yeast cells deficient in 20S proteasome function are connected with the unique Rad6/Rad18-dependent error-prone translesion DNA synthesis (TLS) requiring the activities of both TLS polymerases: Pol eta and Pol zeta. Our results suggest the involvement of proteasomal activity in the limitation of this unique error-prone TLS mechanism in wild-type cells. On the other hand, we found that the mutator phenotypes caused by deficiency in Rad18 and Rad6, are largely alleviated by defects in proteasome activities. Since the mutator phenotypes produced by deletion of RAD6 and RAD18 require Pol zeta and Siz1/Ubc9-dependent sumoylation of PCNA, our results suggest that proteasomal dysfunction limits sumoylation-dependent error-prone activity of Pol zeta. Taken together, our findings strongly support the idea that proteolytic activity is involved in modulating the balance between TLS mechanisms functioning during DNA replication in S. cerevisiae.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk