Altered epigenetic patterning leading to replicative senescence and reduced longevity. A role of a novel SNF2 factor, PASG.
Understanding the biological mechanisms underlying aging and cancer predisposition remains a fundamentally important goal in biomedicine. The generation of a PASG hypomorphic mutant mouse model shows that PASG, an SNF2 family member, is essential for properly maintaining normal DNA methylation and gene expression patterns. Disruption of PASG leads to decreased incorporation of BrdU, accumulation of senescence-associated tumor suppressor genes, and increased senescence-associated beta-galactosidase as well as age-related phenotypes. These observations demonstrate that PASG plays a critical role in maintenance of tissue homeostasis, normal growth and longevity.
Sun
Lin-Quan
LQ
Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Arceci
Robert J
RJ
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D008136:Longevity / Q000235:genetics; D008780:Methyltransferases / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D001616:beta-Galactosidase / Q000378:metabolism
D004247:DNA; D008780:Methyltransferases; D001616:beta-Galactosidase; D004265:DNA Helicases; C487055:Hells protein, mouse; D001973:Bromodeoxyuridine