Human mismatch repair protein hMutLα is required to repair short slipped-DNAs of trinucleotide repeats.

摘要: Mismatch repair (MMR) is required for proper maintenance of the genome by protecting against mutations. The mismatch system has also been implicated as a driver certain mutations, including disease-associated trinucleotide repeat instability. We recently revealed requirement hMutSβ in short slip-outs containing single CTG unit (1). involvement other MMR proteins slip-out unknown. Here we show that hMutLα highly efficient vitro slip-outs, to same degree hMutSβ. HEK293T cell extracts, deficient hMLH1, are unable process single-repeat but functional when complemented with hMutLα. MMR-deficient hMLH1 mutant, T117M, which point mutation proximal ATP-binding domain, defective repair, further supporting processing and possibly hMHL1 ATPase activity. Extracts hPMS2-deficient HEC-1-A cells, express hMLH3, hPMS1, only hMutLα, indicating neither hMutLβ nor hMutLγ sufficient slip-outs. resolution clustered poorly repaired, was partially dependent upon joint suggests instability may be result aberrant outcomes attempts.