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MSH3
DNA mismatch repair protein, MutS Homolog 3 (MSH3) is a human homologue of the bacterial mismatch repair protein MutS that participates in the mismatch repair (MMR) system. MSH3 typically forms the heterodimer MutSβ with MSH2 in order to correct long insertion/deletion loops and base-base mispairs in microsatellites during DNA synthesis. Deficient capacity for MMR is found in approximately 15% of colorectal cancers, and somatic mutations in the MSH3 gene can be found in nearly 50% of MMR-deficient colorectal cancers.
==Gene and Expression==
In humans, the encoding gene for MSH3 is found on chromosome 5 at location 5q11-q12 upstream of the dihydrofolate reductase (DHFR) gene. MSH3 is encoded by 222,341 base pairs and creates a protein consisting of 1137 amino acids.
MSH3 is typically expressed at low levels in several transformed cell lines—including HeLa, K562, HL-60, and CEM—as well as a large range of normal tissues including spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood leukocytes, heart, brain, placenta, lung, liver, skeletal muscle kidney, and pancreas. Although expression levels of MSH3 vary slightly from tissue to tissue, its widespread low-level expression indicates that it is a “housekeeping” gene commonly expressed in all cells.〔
Over-expression of MSH3 decreased capacity for MMR. When MSH3 is over expressed, drastic changes occur in the relative levels of formation of MutSβ at the expense of MutSα. MutSα is responsible for base-base mispairs and short insertion/deletion loops, while MutSβ reapirs long insertion/deletion loops in DNA. A drastic shift in the relative levels of these protein complexes can lead to diminished capacity for MMR. In the case of MSH3 overexpression, MSH2 preferentially heterodimerizes with MSH3 leading to high levels of MutSβ and degradation of the partnerless MSH6 protein which normally complexes with MSH2 to form MutSα.
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
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