Duplicating DNA: how Mms1 interacts with specific DNA motifs to control genome integrity

Scientists of the European Research Institute for the Biology of Ageing discovered that the protein Mms1 interacts with G-rich motifs in the genome that can form stable DNA structures in regulation of DNA replication and genome integrity. The research by Katharina Wanzek and others was performed in the research group led by Katrin Paeschke. On May 23, the research article “Mms1 binds to G-rich regions in Saccharomyces cerevisiae and influences replication and genome stability” was published online in the journal Nucleic Acids Research (https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkx467).

Proper control of DNA replication prior to cell division is essential to preserve genome integrity. Mms1 is part of the protein complex that is linked to progression of the DNA replication machinery. In this paper, the researchers used yeast (Saccharomyces cerevisiae) to identify binding sites for Mms1 in the genome. It was found that Mms1 specifically interacts with particular G-rich motifs. This motifs can form G-quadruplex (G4) structures in vitro. G4 are stable DNA structures that are known to impede replication fork progression. In the absence of Mms1, genome stability is at risk at these G-rich/G4 regions. Mms1 binds throughout the cell cycle to these G-rich/G4 regions and supports the binding of Pif1 DNA helicase that helps in unwinding DNA for replication. Based on these data, a mechanistic model is proposed in which Mms1 binds to specific G-rich/G4 motif located on the lagging strand template for DNA replication and supports Pif1 function, DNA replication and genome integrity