PMS1 postmeiotic segregation increased 1
932 amino acids; about 106 kDa
This gene encodes a protein belonging to
the DNA mismatch repair mutL/hexB family. This protein is thought to be
involved in the repair of DNA mismatches, and it can form heterodimers with
MLH1, a known DNA mismatch repair protein.
Defects in PMS1 are the cause of
hereditary non-polyposis colorectal cancer type 3 (HNPCC3). Mutations in more
than one gene locus can be involved alone or in combination in the production
of the HNPCC phenotype (also called Lynch syndrome). Most families with
clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC
is an autosomal, dominantly inherited disease associated with marked increase
in cancer susceptibility. It is characterized by a familial predisposition to
early onset colorectal carcinoma (CRC) and extra-colonic cancers of the
gastrointestinal, urological and female reproductive tracts. HNPCC is reported
to be the most common form of inherited colorectal cancer in the Western world,
and accounts for 15% of all colon cancers. Cancers in HNPCC originate within
benign neoplastic polyps termed adenomas.
Clinically, HNPCC is often divided into
Type I: hereditary predisposition to
colorectal cancer, a young age of onset, and carcinoma observed in the proximal
Type II: patients have an increased risk
for cancers in certain tissues such as the uterus, ovary, breast, stomach,
small intestine, skin, and larynx in addition to the colon. Diagnosis of
classical HNPCC is based on the Amsterdam
3 or more relatives affected by colorectal
cancer, one a first degree relative of the other two;
2 or more generation affected;
1 or more colorectal cancers presenting
before 50 years of age; exclusion of hereditary polyposis syndromes.
The term 'suspected HNPCC' or 'incomplete
HNPCC' can be used to describe families who do not or only partially fulfill
criteria, but in whom a genetic basis for colon cancer is strongly suspected.
References (open access):
Characterization of the interactome of the
human MutL homologues MLH1, PMS1, and PMS2. Cannavo E, Gerrits B, Marra G,
Schlapbach R, Jiricny J. J Biol Chem. 2007 Feb 2;282(5):2976-86.
A conserved MutS homolog connector domain
interface interacts with MutL homologs. Mendillo ML, Hargreaves VV, Jamison JW,
Mo AO, Li S, Putnam CD, Woods VL Jr, Kolodner RD. Proc Natl
Acad Sci U S A. 2009 Dec 29;106(52):22223-8.