DNA hypomethylation leads to elevated mutation rates

摘要: Genome-wide demethylation has been suggested to be a step in carcinogenesis. Evidence for this notion comes from the frequently observed global DNA hypomethylation tumour cells, and recent study suggesting that defects methylation might contribute genomic instability of some colorectal cell lines. also associated with abnormal chromosomal structures, as cells patients ICF (Immunodeficiency, Centromeric Facial abnormalities) syndrome treated demethylating agent 5-azadeoxycytidine. Here we report murine embryonic stem nullizygous major methyltransferase (Dnmt1) gene exhibited significantly elevated mutation rates at both endogenous hypoxanthine phosphoribosyltransferase (Hprt) an integrated viral thymidine kinase (tk) transgene. Gene deletions were predominant mutations loci. The cause tk was either mitotic recombination or loss accompanied by duplication remaining chromosome. Our results imply important role mammalian maintaining genome stability.