Biomaterial Database

Constitutive deficiency in DNA mismatch repair. 2007

K E A Felton, and D M Gilchrist, and S E Andrew

Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.

Mutations in the DNA mismatch repair (MMR) genes are associated with the inheritance of hereditary non-polyposis colorectal cancer, also known as Lynch syndrome, a cancer syndrome with an average age at onset of 44. Individuals presenting with colorectal cancer are diagnosed with Lynch I, whereas individuals who present with extra-colonic tumors (such as endometrial, stomach, etc.) are identified as patients with Lynch syndrome II. Recently, 30 families have been reported with inheritance of biallelic mutations in the MMR genes. Here we summarize the phenotype of individuals with inheritance of homozygous or compound heterozygous mutations in the MMR genes that result in a complete lack of protein or greatly compromised protein function. In contrast to individuals with Lynch syndrome I and II, individuals with no MMR function present with childhood onset of hematological and brain malignancies, whereas residual MMR function can also result in gastrointestinal cancers and an age of onset in the second to fourth decade. Individuals with biallelic MMR mutations often present with café-au-lait spots, regardless of the level of MMR function remaining. Thus, the inheritance of two MMR gene mutations is a separate entity from Lynch I or II or the subtypes Turcot and Muir-Torre.

UI	MeSH Term	Description	Entries
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D009687	Nuclear Proteins	Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.	Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D003123	Colorectal Neoplasms, Hereditary Nonpolyposis	A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.	Colon Cancer, Familial Nonpolyposis, Type 1,Colorectal Cancer, Hereditary Nonpolyposis, Type 1,Familial Nonpolyposis Colon Cancer Type 1,Hereditary Nonpolyposis Colorectal Cancer,Hereditary Nonpolyposis Colorectal Cancer Type 1,Hereditary Nonpolyposis Colorectal Neoplasms,Lynch Syndrome,Colon Cancer, Familial Nonpolyposis,Colorectal Cancer Hereditary Nonpolyposis,Familial Nonpolyposis Colon Cancer,Hereditary Nonpolyposis Colon Cancer,Lynch Cancer Family Syndrome I,Lynch Syndrome I,Syndrome, Lynch
D004268	DNA-Binding Proteins	Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.	DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000070957	MutL Protein Homolog 1	Eukaryotic homolog of the bacterial MutL DNA MISMATCH REPAIR protein. It heterodimerizes with MISMATCH REPAIR ENDONUCLEASE PMS2 to form MutL alpha, which is recruited to DNA mismatch sites by the MUTS DNA MISMATCH-BINDING PROTEIN. Mutations in the human MLH1 gene are associated with COLORECTAL NEOPLASMS, HEREDITARY NONPOLYPOSIS.	COCA2 Protein,Colon Cancer, Nonpolyposis Type 2 Protein,MLH1 Protein,MutL Homolog 1
D000070976	Mismatch Repair Endonuclease PMS2	A MutL protein and component of the DNA MISMATCH REPAIR system. Its ENDONUCLEASE activity introduces SINGLE-STRAND DNA BREAKS which create entry points for EXO1 exonuclease to remove the strand containing the mismatch. It may also function in DNA DAMAGE signaling.	PMS-2 Protein,PMS1 Homolog 2, Mismatch Repair Protein,PMS2 Protein,Postmeiotic Segregation Increased-S. cerevisiae-2,PMS 2 Protein,Postmeiotic Segregation Increased S. cerevisiae 2
D000251	Adenosine Triphosphatases	A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.	ATPases,Adenosinetriphosphatase,ATPase,ATPase, DNA-Dependent,Adenosine Triphosphatase,DNA-Dependent ATPase,DNA-Dependent Adenosinetriphosphatases,ATPase, DNA Dependent,Adenosinetriphosphatases, DNA-Dependent,DNA Dependent ATPase,DNA Dependent Adenosinetriphosphatases,Triphosphatase, Adenosine
D045643	DNA Repair Enzymes	Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.	DNA Repair Enzyme,Enzyme, DNA Repair,Enzymes, DNA Repair,Repair Enzyme, DNA,Repair Enzymes, DNA
D048868	Adaptor Proteins, Signal Transducing	A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes	Signal Transducing Adaptor Proteins