New facet of DNA mismatch repair discovered
5-methylcytosine is a methylated form of the DNA base cytosine that regulates gene transcription and has several other biological roles.
Spontaneous deamination of 5-methylcytosine is a common form of DNA damage occurring in our cells hundreds of times every day. The reaction, if detected before replication can be corrected by the enzyme thymine-DNA glycosylase. This type of repair is known as non-replication associated DNA repair.
Scientists at the University of Hong Kong have revealed some of the complexities of non-replication associated DNA repair. In Science Advances, they show that DNA mismatch repair, a mechanism previously associated with errors occurring during replication itself, also has a role in non replication associated repair processes.
DNA mismatch repair recognises and repairs the erroneous insertion, deletion, and mis-incorporation of bases that can arise during DNA replication and recombination. Dr Jason Wong Wing-hon, an associate professor at the School of Biomedical Sciences at the Faculty of Medicine at the University of Hong Kong, and his colleagues were able to show that DNA mismatch repair also plays an important role in 5-methylcytosine deamination.
The research team used somatic mutation data from several cohorts of cancer patients to resolve the key mutational processes associated with the loss of specific components of the mismatch repair process. They then integrated epigenetic data and somatic mutations from cancers with specific defects in both non-replication and replication-associated DNA repair.
“Our findings revealed a previously unknown role of mismatch repair that is essential in protecting the human genome from damage induced by 5-methylcytosine deamination,” said Dr Jason Wong Wing-hon, Associate Professor of the School of Biomedical Sciences at the Faculty of Medicine at the University of Hong Kong, who initiated the study.
