Derevensky Michael, Fasullo Michael
College of Nanoscale Sciences and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, NY 12205, United States.
College of Nanoscale Sciences and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, NY 12205, United States.
Mutat Res Genet Toxicol Environ Mutagen. 2018 Nov;835:16-20. doi: 10.1016/j.mrgentox.2018.08.007. Epub 2018 Aug 24.
Many DNA damaging agents also react with RNA and protein, and could thus cause epigenetic as well as genotoxic changes. To investigate which DNA damaging agents alter epigenetic states, we studied the chemical-induced changes in expression of the yeast silent mating type locus HMLα, which can be triggered by inhibiting yeast Sir2. We observed that the alkylating agent methyl methane sulfonate (MMS) can result in HMLα expression, using a colony sector assay that results from expression of a HML-positioned cre gene. Using single-cell imaging we also observed that alkylating agents, including MMS and methyl-3-nitro-1-nitrosoguanidine (MNNG), as well as short-wave UV, also decreased HML silencing. We suggest that chemical-induced alterations in heterochromatin structure could confer transient phenotypic changes that affect the cellular responses to DNA damaging agents.
许多DNA损伤剂也会与RNA和蛋白质发生反应,因此可能导致表观遗传变化以及基因毒性变化。为了研究哪些DNA损伤剂会改变表观遗传状态,我们研究了化学诱导的酵母沉默交配型基因座HMLα表达的变化,这种变化可通过抑制酵母Sir2来触发。我们观察到,使用由HML定位的cre基因表达产生的菌落扇形分析,烷基化剂甲磺酸甲酯(MMS)可导致HMLα表达。通过单细胞成像我们还观察到,包括MMS和甲基-3-硝基-1-亚硝基胍(MNNG)在内的烷基化剂,以及短波紫外线,也会降低HML的沉默。我们认为,化学诱导的异染色质结构改变可能会赋予短暂的表型变化,从而影响细胞对DNA损伤剂的反应。