Histone-lysine N-methyltransferase SETD2 (SETD2)

Histone methyltransferase that specifically trimethylates'Lys-36' of histone H3 (H3K36me3) with dimethylated'Lys-36' (H3K36me2) as substrate (PubMed:16118227, PubMed:19141475, PubMed:21526191, PubMed:21792193, PubMed:23043551, PubMed:27474439). Represents the main receptor producing H3K36me3, a particular tag for epigenetic transcriptional activation (By similarity).

Acts as a key regulator of DNA mismatch repair in G1 and early S phase by producing H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction (PubMed:23622243). Required for DNA double-strand fracture repair in response to DNA damage: acts by mediating creation of H3K36me3, boosting recruitment of RAD51 and DNA repair via homologous recombination (HR) (PubMed:24843002).