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This interaction promotes the timely recruitment of MutSα to chromatin in G1 and early S phases, and it appears to coordinate repair activity with other DNA repair pathways, for example, by enhancing the glycosylase activity of hMYH in the correction of oxidatively damaged bases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGermline mutations in MSH6 account for a substantial subset of Lynch syndrome cases and are associated with an altered spectrum of cancer risk. Individuals harboring MSH6 defects often develop colorectal and endometrial cancers with later onset relative to mutations in other MMR genes, and emerging data also implicate MSH6 mutations in predisposition to cancers of the prostate, brain, and other extracolonic sites. Moreover, both inherited and somatic inactivation of MSH6 has been linked to a hypermutated phenotype in tumors such as recurrent glioblastomas and advanced prostate carcinomas, influencing treatment resistance and clinical outcomes. Collectively, these studies underscore the pivotal role of MSH6 in genome maintenance and its importance as a genetic determinant of cancer risk."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "34"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe assessment of MSH6 expression through immunohistochemical analysis is integral to the diagnostic workup for MMR deficiency in tumors. Altered or diminished MSH6 staining patterns—as sometimes observed in post‐treatment colorectal carcinomas—complement microsatellite instability testing and help identify patients who may harbor Lynch syndrome. 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