title: Mismatch repair pathway: molecules, functions, and role in colorectal carcinogenesis.
abstract: The microsatellite instability (MSI) pathway is one of the important mutational pathways that play a critical role in colorectal carcinogenesis. About 15% of colorectal cancers (CRCs) are characterized by MSI. MSI tumors usually arise because of a genetic defect in mismatch repair (MMR) genes, one of the main DNA-repairing systems. MMR is a highly conserved biological pathway that plays a key role in maintaining genomic stability by correcting the base-base mismatches and insertion/deletion mispairs generated during DNA replication and recombination. Escherichia coli MutS and MutL and their eukaryotic homologs, MutSα and MutLα, respectively, are key players in MMR-associated genome maintenance. Mutations in at least five pivotal genes of MMR, namely, in those encoding mutS homolog 2 (MSH2), mutL homolog 1 (MLH1), mutS homolog 6 (MSH6), postmeiotic segregation increased 1 (PMS1), and postmeiotic segregation, increased 2 (PMS2) have been found in CRC, highlighting the importance of understanding the basic structure and functions of the essential molecules that make up the MMR system. In this review, we have attempted to focus on this aspect, that is, the role that MMR molecules play in CRC carcinogenesis.
authors.affiliation: aDepartment of Biochemistry, Sher-I-Kashmir Institute of Medical Sciences Associated Medical College Departments of bBiochemistry cBiotechnology, Kashmir University, Srinagar, Kashmir, India.
authors.forename: Aga Syed
authors.initials: AS
authors.lastname: Sameer
authors.forename: Saniya
authors.initials: S
authors.lastname: Nissar
authors.forename: Kaneez
authors.initials: K
authors.lastname: Fatima
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000251:Adenosine Triphosphatases / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D018450:Disease Progression; D006801:Humans; D053842:Microsatellite Instability; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein / Q000235:genetics; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; C500929:MutLalpha protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C088996:PMS1 protein, human; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes