Human DNA polymerase α interacts with mismatch repair proteins MSH2 and MSH6.
High fidelity of genome duplication is ensured by cooperation of polymerase proofreading and mismatch repair (MMR) activities. Here, we show that human mismatch recognizing proteins MutS homolog 2 (MSH2) and MSH6 copurify and interact with replicative Pol α. This enzyme also is the replicative primase and replicates DNA with poor fidelity. We show that MSH2 associates with known human replication origins with different dynamics than DNA polymerase (Pol α). Furthermore, we explored the potential functional role of Pol α in the mismatch repair reaction using an in vitro mismatch repair assay and observed that Pol α promotes mismatch repair. Taken together, we show that human Pol α interacts with MSH2-MSH6 complex and propose that this interaction occurs during the mismatch repair reaction.
Research group Biochemistry, Leibniz Institute on Aging - Fritz Lipmann Institute, Jena, Germany.|Department of Biology, University of Eastern Finland, Joensuu, Finland.|Prostate Cancer Research Group, Nordic EMBL Partnership, Centre for Molecular Medicine Norway, University of Oslo, Blindern, Norway.
Harri M
HM
Itkonen
Department of Biosciences, Division of Genetics, University of Helsinki, Finland.
Jukka
J
Kantelinen
Department of Biology, University of Eastern Finland, Joensuu, Finland.
Markku
M
Vaara
Department of Biology, University of Eastern Finland, Joensuu, Finland.
Sinikka
S
Parkkinen
Research group Biochemistry, Leibniz Institute on Aging - Fritz Lipmann Institute, Jena, Germany.|Service group Proteomics, Leibniz Institute on Aging - Fritz Lipmann Institute, Jena, Germany.
Bernhard
B
Schlott
Research group Biochemistry, Leibniz Institute on Aging - Fritz Lipmann Institute, Jena, Germany.
Frank
F
Grosse
Department of Biosciences, Division of Genetics, University of Helsinki, Finland.
Minna
M
Nyström
Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Juhani E
JE
Syväoja
Research group Biochemistry, Leibniz Institute on Aging - Fritz Lipmann Institute, Jena, Germany.|Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland.
Helmut
H
Pospiech
D053843:DNA Mismatch Repair; D004256:DNA Polymerase I / Q000378:metabolism*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051718:MutS Homolog 2 Protein / Q000378:metabolism*; D011485:Protein Binding; D013379:Substrate Specificity
D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D004256:DNA Polymerase I; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein
DNA mismatch repair; DNA replication; chromatin immunoprecipitation