This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lau, P. J. Articles by Kolodner, R. D. Search for Related Content PubMed PubMed Citation Articles by Lau, P. J. Articles by Kolodner, R. D.

Isolation and Characterization of New Proliferating Cell Nuclear Antigen (POL30) Mutator Mutants That Are Defective in DNA Mismatch Repair

Ludwig Institute for Cancer Research, Cancer Center, and Department of Medicine, University of California-San Diego School of Medicine, La Jolla, California 92093-0660

Received 28 February 2002/ Returned for modification 31 March 2002/ Accepted 28 June 2002

A number of studies have suggested a role for proliferating cell nuclear antigen (PCNA) in DNA mismatch repair (MMR). However, the majority of mutations in the POL30 gene encoding PCNA that cause MMR defects also cause replication and other repair defects that contribute to the increased mutation rate caused by these mutations. Here, 20 new pol30 mutants were identified and screened for MMR and other defects, resulting in the identification of two mutations, pol30-201 and pol30-204, that appear to cause MMR defects but little if any other defects. The pol30-204 mutation altered an amino acid (C81R) in the monomer-monomer interface region and resulted in a partial general MMR defect and a defect in MSH2-MSH6 binding in vitro. The pol30-201 mutation altered an amino acid (C22Y) located on the surface of the PCNA trimer that slides over the DNA but did not cause a defect in MSH2-MSH6 binding in vitro. The pol30-201 mutation caused an intermediate mutator phenotype. However, the pol30-201 mutation caused almost a complete defect in the repair of AC and GT mispairs and only a small defect in the repair of a "+T" insertion, an effect similar to that caused by an msh6 mutation, indicating that pol30-201 primarily effects MSH6-dependent MMR. The chromosomal double mutant msh3-FF>AA msh6-FF>AA eliminating the conserved FF residues of the PCNA interacting motif of these proteins caused a small (<10%) defect in MMR but showed synergistic interactions with mutations in POL30, indicating that the FF>AA substitution may not eliminate PCNA interactions in vivo. These results indicate that the interaction between PCNA and MMR proteins is more complex than was previously appreciated.

This article has been cited by other articles:

• Xu, X., Page, J. L., Surtees, J. A., Liu, H., Lagedrost, S., Lu, Y., Bronson, R., Alani, E., Nikitin, A. Yu., Weiss, R. S. (2008). Broad Overexpression of Ribonucleotide Reductase Genes in Mice Specifically Induces Lung Neoplasms. Cancer Res. 68: 2652-2660 [Abstract] [Full Text]  
• Stone, J. E., Ozbirn, R. G., Petes, T. D., Jinks-Robertson, S. (2008). Role of Proliferating Cell Nuclear Antigen Interactions in the Mismatch Repair-Dependent Processing of Mitotic and Meiotic Recombination Intermediates in Yeast. Genetics 178: 1221-1236 [Abstract] [Full Text]  
• Masih, P. J., Kunnev, D., Melendy, T. (2008). Mismatch Repair proteins are recruited to replicating DNA through interaction with Proliferating Cell Nuclear Antigen (PCNA). Nucleic Acids Res 36: 67-75 [Abstract] [Full Text]  
• Kow, Y. W., Bao, G., Reeves, J. W., Jinks-Robertson, S., Crouse, G. F. (2007). Oligonucleotide transformation of yeast reveals mismatch repair complexes to be differentially active on DNA replication strands. Proc. Natl. Acad. Sci. USA 104: 11352-11357 [Abstract] [Full Text]  
• Jiang, C., Hwang, Y. T., Randell, J. C. W., Coen, D. M., Hwang, C. B. C. (2007). Mutations That Decrease DNA Binding of the Processivity Factor of the Herpes Simplex Virus DNA Polymerase Reduce Viral Yield, Alter the Kinetics of Viral DNA Replication, and Decrease the Fidelity of DNA Replication. J. Virol. 81: 3495-3502 [Abstract] [Full Text]  
• Ivanov, I., Chapados, B. R., McCammon, J. A., Tainer, J. A. (2006). Proliferating cell nuclear antigen loaded onto double-stranded DNA: dynamics, minor groove interactions and functional implications. Nucleic Acids Res 34: 6023-6033 [Abstract] [Full Text]  
• de Saro, F. J. L., Marinus, M. G., Modrich, P., O'Donnell, M. (2006). The beta Sliding Clamp Binds to Multiple Sites within MutL and MutS. J. Biol. Chem. 281: 14340-14349 [Abstract] [Full Text]  
• Erdeniz, N., Dudley, S., Gealy, R., Jinks-Robertson, S., Liskay, R. M. (2005). Novel PMS1 Alleles Preferentially Affect the Repair of Primer Strand Loops during DNA Replication. Mol. Cell. Biol. 25: 9221-9231 [Abstract] [Full Text]  
• Lau, P. J., Kolodner, R. D. (2003). Transfer of the MSH2{middle dot}MSH6 Complex from Proliferating Cell Nuclear Antigen to Mispaired Bases in DNA. J. Biol. Chem. 278: 14-17 [Abstract] [Full Text]