Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis

Asad Umar, Andrew B. Buermeyer, Jeffrey A. Simon, David C. Thomas, Alan B. Clark, Robert (Mike) Liskay, Thomas A. Kunkel

Research output: Contribution to journalArticle

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Abstract

A two-hybrid system was used to screen yeast and human expression libraries for proteins that interact with mismatch repair proteins. PCNA was recovered from both libraries and shown in the case of yeast to interact with both MLH1 and MSH2. A yeast strain containing a mutation in the PCNA gene had a strongly elevated mutation rate in a dinucleotide repeat, and the rate was not further elevated in a strain also containing a mutation in MLH1. Mismatch repair activity was examined in human cell extracts using an assay that does not require DNA repair synthesis. Activity was inhibited by p21WAF1 or a p21 peptide, both of which bind to PCNA, and activity was restored to inhibited reactions by addition of PCNA. The data suggest a PCNA requirement in mismatch repair at a step preceding DNA resynthesis. The ability of PCNA to bind to MLH1 and MSH2 may reflect linkage between mismatch repair and replication and may be relevant to the roles of mismatch repair proteins in other DNA transactions.

Original languageEnglish (US)
Pages (from-to)65-73
Number of pages9
JournalCell
Volume87
Issue number1
DOIs
StatePublished - Oct 1996

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DNA Mismatch Repair
Proliferating Cell Nuclear Antigen
Repair
DNA
Yeast
Yeasts
Dinucleotide Repeats
Mutation
Proteins
Mutation Rate
Cell Extracts
Hybrid systems
DNA Repair
Libraries
Assays
Genes
Cells
Peptides

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Umar, A., Buermeyer, A. B., Simon, J. A., Thomas, D. C., Clark, A. B., Liskay, R. M., & Kunkel, T. A. (1996). Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis. Cell, 87(1), 65-73. https://doi.org/10.1016/S0092-8674(00)81323-9

Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis. / Umar, Asad; Buermeyer, Andrew B.; Simon, Jeffrey A.; Thomas, David C.; Clark, Alan B.; Liskay, Robert (Mike); Kunkel, Thomas A.

In: Cell, Vol. 87, No. 1, 10.1996, p. 65-73.

Research output: Contribution to journalArticle

Umar, A, Buermeyer, AB, Simon, JA, Thomas, DC, Clark, AB, Liskay, RM & Kunkel, TA 1996, 'Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis', Cell, vol. 87, no. 1, pp. 65-73. https://doi.org/10.1016/S0092-8674(00)81323-9
Umar A, Buermeyer AB, Simon JA, Thomas DC, Clark AB, Liskay RM et al. Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis. Cell. 1996 Oct;87(1):65-73. https://doi.org/10.1016/S0092-8674(00)81323-9
Umar, Asad ; Buermeyer, Andrew B. ; Simon, Jeffrey A. ; Thomas, David C. ; Clark, Alan B. ; Liskay, Robert (Mike) ; Kunkel, Thomas A. / Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis. In: Cell. 1996 ; Vol. 87, No. 1. pp. 65-73.
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