Msh2-flox Mouse

Msh2, short for MutS homolog 2, is an essential gene involved in DNA mismatch repair (MMR) pathway [1,3,4,5,6,7,8,9]. The proteins encoded by Msh2, as a part of complexes like MutSα (MSH2-MSH6) and MutSβ (MSH2-MSH3), are crucial for recognizing and repairing DNA mismatches, thus maintaining genome stability [7,9]. MMR deficiency can lead to cancer development and impacts cancer cell response to chemotherapy [7].

In Arabidopsis, Msh2 acts as a master regulator of meiotic DSB repair, stimulating interfering crossovers and inhibiting non-interfering crossovers in response to genetic polymorphism [2]. In Saccharomyces cerevisiae, the Msh2-Msh3 complex not only functions in post-replicative MMR but also contributes to genome stability through homologous recombination, double-strand break repair, and the DNA damage response, yet it can also promote genome instability through trinucleotide repeat expansions [3]. In human colorectal cancer cell lines, a methylation tolerance-based functional assay can assess the effects of variants of unknown significance (VUS) in Msh2 on DNA MMR, which may help in identifying patients with Lynch syndrome [1]. In bladder cancer, Msh2 is a mediator of cisplatin sensitivity, and circLIFR can synergize with Msh2 to positively modulate cisplatin-sensitivity through the MutSα/ATM-p73 axis [4]. Loss of Msh2 protein in primary prostate cancer is correlated with Msh2 inactivation, hypermutation, and higher tumor-infiltrating lymphocyte density, especially common in very high-grade primary tumors [8].

In conclusion, Msh2 is vital for DNA mismatch repair and genome stability. Its functions are revealed through studies in various organisms and cell lines. Defects in Msh2 are associated with multiple diseases, especially cancers like Lynch syndrome-associated endometrial cancer, bladder cancer, and prostate cancer. Understanding Msh2 helps in comprehending disease mechanisms and may potentially guide cancer treatment strategies.