How does mammalian DNA repair mechanisms prevent cancer? This review explores the critical role of DNA mismatch repair (MMR) in maintaining genomic stability in mammalian cells. The study emphasizes the importance of MMR, alongside other replication, repair, and recombination processes, for both prokaryotes and eukaryotes. Following the discovery that mutations in MMR genes are linked to hereditary nonpolyposis colorectal cancer (HNPCC) and other cancers, the biochemical functions of mammalian MutS and MutL homologs have come under close scrutiny. Through genetic studies in cultured mammalian cells and mice, researchers are defining the relationship between MMR functions and the avoidance of mutations and tumors. Genetic research has revealed that MMR homologs contribute to DNA damage surveillance, transcription-coupled repair, and recombinogenic and meiotic processes. These genetic insights shed light on the connection between MMR gene defects and the development of various human cancers. These studies reveal that MMR homologs play a crucial role in maintaining genomic integrity and preventing tumorigenesis. The findings highlight the significance of MMR pathways in understanding and potentially treating cancers associated with defects in these genes.
Published in the Annual Review of Genetics, this article aligns with the journal's focus on providing comprehensive overviews of key topics in genetics. The review of mammalian DNA mismatch repair (MMR) contributes to the understanding of genome stability, mutation avoidance, and cancer prevention, all central themes within the field of genetics.