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Downregulation of methyltransferase Dnmt2 results in condition‐dependent telomere shortening and senescence or apoptosis in mouse fibroblasts
Author(s) -
Lewinska Anna,
AdamczykGrochala Jagoda,
Kwasniewicz Ewa,
Wnuk Maciej
Publication year - 2017
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25848
Subject(s) - telomere , senescence , telomerase , dna damage , downregulation and upregulation , gene knockdown , dna methylation , telomerase reverse transcriptase , biology , reactive oxygen species , gene silencing , methyltransferase , apoptosis , chemistry , microbiology and biotechnology , methylation , genetics , dna , gene expression , gene
Dnmt2 is a highly conserved methyltransferase of uncertain biological function(s). As Dnmt2 was considered as a driver of fruit fly longevity and a modulator of stress response, we decided to evaluate the role of Dnmt2 during stress‐induced premature senescence in NIH3T3 mouse fibroblasts. Stable knockdown of Dnmt2 resulted in hydrogen peroxide‐mediated sensitivity and apoptosis, whereas in the control conditions, senescence was induced. Cellular senescence was accompanied by elevated levels of p53 and p21, decreased telomere length and telomerase activity, increased production of reactive oxygen species and protein carbonylation, and DNA damage. Dnmt2 silencing also promoted global DNA and RNA hypermethylation, and upregulation of methyltransferases, namely Dnmt1, Dnmt3a, and Dnmt3b. Taken together, we show for the first time that Dnmt2 may promote lifespan in the control conditions and survival during stress conditions in mouse fibroblasts.