About Minttu


eLS: Mismatch Repair Genes

Kansikas M, Nyström M & Peltomäki P.

The mismatch repair (MMR) system is necessary for the maintenance of genomic stability. The primary role of MMR is to correct errors such as base/base mismatches and small insertions/deletions that arise during DNA (deoxyribonucleic acid) synthesis. Loss of functional MMR results in increased rates of point mutations and microsatellite instability. Post-replicative MMR is strand-specific and serves mutation avoidance. Outside replication, discrimination between old and newly synthesised DNA strands is no longer necessary, and the MMR system can be mutagenic. Such non-canonical actions of MMR are required, for example, for the generation of immunoglobulin diversity. The anti-mutator and mutator activities of MMR play important roles in human diseases. Notably, germline mutations in MMR genes cause predisposition to Lynch syndrome, whereas epigenetic inactivation of the MMR gene MLH1 underlies 15% of sporadic colorectal and other cancers.


Link to updated article. eLS, 2017.


Nobel Lecture 2015 on DNA repair

Professor Nyström has the honour of delivering the Nobel Lecture 2015 in recognition of Professor Lindahl, Modrich and Sancar and their Chemistry 2015 Nobel prize winning work “For mechanistic studies of DNA repair”.

The lecture will be held together with Professor Meri’s lecture on the Physiology or Medicine Nobel prize winners works.

The lectures will be delivered on Wednesday, October 21st, 11.00-12.00 in Biocenter 2, Lecture hall 2041.

Using the in vitro MMR assay to recognize reduced MMR gene expression levels

Assessing how reduced expression levels of the mismatch repair genes MLH1, MSH2 and MSH6 affect repair efficiency

Minttu Kansikas, Mariann Kasela, Jukka Kantelinen and Minna Nyström

Lynch syndrome (LS), the most common familial colon cancer, is associated with mismatch repair (MMR) malfunction. As mutation carriers inherit one normal and one defected MMR gene allele, cancer risk can be considered as limited amount of normal MMR gene product. How reductions in different MMR gene expressions affect MMR capability is, however, not known. The in vitro MMR assay is a method for the pathogenicity assessment of MMR gene variants causing functional or expressional defects and thus also suitable to evaluate the effects of reduced expression of normal mRNA. Here, the assay was applied to quantify repair efficiencies of human cells retaining varying expression levels (25%/50%/75%) of the main LS susceptibility genes MLH1,MSH2 or MSH6. Compared to the shRNA knockdown control, already a 50% reduction in mRNA levels could be detected as decreased MMR function although without statistical significance in MLH1. In MSH2 and MLH1, total loss of MMR was achieved with 25% expression, while in MSH6 and MSH2 the repair capability decreased significantly already with 75% expression. Our results provide a preliminary indication of relative expressions required for wild-type function and suggest that the in vitro MMR assay could be used to recognize expression levels indicative of LS.

Human Mutation, 2014.