Molecular cell, 2015-09, Vol.59 (5), p.831-839
2015
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Details
- Autor(en) / Beteiligte
- Titel
- MCM9 Is Required for Mammalian DNA Mismatch Repair
- Ist Teil von
- Molecular cell, 2015-09, Vol.59 (5), p.831-839
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- DNA mismatch repair (MMR) is an evolutionarily conserved process that corrects DNA polymerase errors during replication to maintain genomic integrity. In E. coli, the DNA helicase UvrD is implicated in MMR, yet an analogous helicase activity has not been identified in eukaryotes. Here, we show that mammalian MCM9, a protein involved in replication and homologous recombination, forms a complex with MMR initiation proteins (MSH2, MSH3, MLH1, PMS1, and the clamp loader RFC) and is essential for MMR. Mcm9−/− cells display microsatellite instability and MMR deficiency. The MCM9 complex has a helicase activity that is required for efficient MMR since wild-type but not helicase-dead MCM9 restores MMR activity in Mcm9−/− cells. Moreover, MCM9 loading onto chromatin is MSH2-dependent, and in turn MCM9 stimulates the recruitment of MLH1 to chromatin. Our results reveal a role for MCM9 and its helicase activity in mammalian MMR. [Display omitted] •MCM9 associates with MMR initiation proteins•MCM9 is required for the MMR reaction•The MCM9 complex carries a DNA helicase activity required for MMR•MCM9 loading onto chromatin requires MSH2 and is involved in MLH1 recruitment MCM9 has functions in replication and homologous recombination. Traver et al. find that it also associates with MMR proteins and that MCM9 and its helicase activity are essential for mismatch repair in cells. MCM9 loading is MSH2 dependent and stimulates the recruitment of MLH1 to chromatin.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1097-2765eISSN: 1097-4164DOI: 10.1016/j.molcel.2015.07.010Titel-ID: cdi_hal_primary_oai_HAL_hal_02361154v1
- Format
- –
- Schlagworte
- Adaptor Proteins, Signal Transducing - chemistry, Adaptor Proteins, Signal Transducing - genetics, Adaptor Proteins, Signal Transducing - metabolism, Base Sequence, Cellular Biology, Chromatin - genetics, Chromatin - metabolism, DNA - genetics, DNA - metabolism, DNA Helicases - chemistry, DNA Helicases - genetics, DNA Helicases - metabolism, DNA Mismatch Repair - genetics, DNA Mismatch Repair - physiology, DNA-Binding Proteins - chemistry, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, Gene Knockout Techniques, HeLa Cells, Humans, Life Sciences, Microsatellite Instability, Minichromosome Maintenance Proteins - deficiency, Minichromosome Maintenance Proteins - genetics, Minichromosome Maintenance Proteins - metabolism, MutL Protein Homolog 1, MutS Homolog 2 Protein - chemistry, MutS Homolog 2 Protein - genetics, MutS Homolog 2 Protein - metabolism, MutS Homolog 3 Protein, Nuclear Proteins - chemistry, Nuclear Proteins - genetics, Nuclear Proteins - metabolism