MSH2: A Potential Drug Target for Cancer and Other Diseases (G4436)

Target Name: MSH2

NCBI ID: G4436

MSH2: A Potential Drug Target for Cancer and Other Diseases

MSH2 (MutL homolog 2) is a gene that encodes a protein known as MSH2 protein. This protein plays a critical role in the regulation of multiple synchronized DNA replication in eukaryotic cells. MSH2 protein has been identified as a potential drug target and biomarker for various diseases, including cancer, neurodegenerative diseases, and autoimmune disorders.

The MSH2 gene is located on chromosome 18 and encodes a protein of 23.5 kDa. The protein is composed of several subunits, each of which plays a distinct role in the regulation of DNA replication. The most well-studied subunit is the alpha subunit, which contains the protein's catalytic active site and is responsible for the binding of DNA replication factors.

The MSH2 protein has been shown to play a critical role in the regulation of multiple synchronized DNA replication. During DNA replication, the MSH2 protein helps to ensure that each new DNA strand is synthesized with the correct sequence and that the replication process is completed efficiently. The MSH2 protein also helps to prevent errors from occurring during DNA replication by recognizing and correcting mistakes that may occur during the replication process.

In addition to its role in DNA replication, the MSH2 protein has also been shown to play a critical role in the regulation of cell growth and division. The MSH2 protein helps to ensure that cells divide in a synchronized and orderly manner, and it also helps to prevent cells from growing out of control.

The MSH2 protein has also been shown to be involved in the regulation of gene expression. The MSH2 protein has been shown to interact with several transcription factors, including DNA-binding proteins such as TF-1 and MBF. These interactions help to ensure that the MSH2 protein is able to recruit these transcription factors to the DNA and facilitate the transcription of their target genes.

The MSH2 protein has also been shown to play a critical role in the regulation of DNA damage repair. The MSH2 protein helps to ensure that cells are able to repair damage to their DNA and prevent the accumulation of mutations that can lead to cancer.

In conclusion, the MSH2 protein is a critical regulator of multiple synchronized DNA replication in eukaryotic cells. Its role in DNA replication, cell growth and division, and gene expression have been well-studied, and it has been shown to play a critical role in the regulation of multiple diseases, including cancer, neurodegenerative diseases, and autoimmune disorders. Therefore, the MSH2 protein is an attractive drug target and biomarker for various diseases.

Protein Name: MutS Homolog 2

Functions: Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. Recruits DNA helicase MCM9 to chromatin which unwinds the mismatch containing DNA strand (PubMed:26300262). ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis

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