title: Depletion of nuclear histone H2A variants is associated with chronic DNA damage signaling upon drug-evoked senescence of human somatic cells.
abstract: Cellular senescence is associated with global chromatin changes, altered gene expression, and activation of chronic DNA damage signaling. These events ultimately lead to morphological and physiological transformations in primary cells. In this study, we show that chronic DNA damage signals caused by genotoxic stress impact the expression of histones H2A family members and lead to their depletion in the nuclei of senescent human fibroblasts. Our data reinforce the hypothesis that progressive chromatin destabilization may lead to the loss of epigenetic information and impaired cellular function associated with chronic DNA damage upon drug-evoked senescence. We propose that changes in the histone biosynthesis and chromatin assembly may directly contribute to cellular aging. In addition, we also outline the method that allows for quantitative and unbiased measurement of these changes.
authors.affiliation: BRIMS, Thermo Fisher Scientific, Cambridge, MA, USA.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Lopez
authors.forename: James
authors.initials: J
authors.lastname: Tollervey
authors.forename: Bryan
authors.initials: B
authors.lastname: Krastins
authors.forename: Alejandra
authors.initials: A
authors.lastname: Garces
authors.forename: David
authors.initials: D
authors.lastname: Sarracino
authors.forename: Amol
authors.initials: A
authors.lastname: Prakash
authors.forename: Maryann
authors.initials: M
authors.lastname: Vogelsang
authors.forename: Glenn
authors.initials: G
authors.lastname: Geesman
authors.forename: Augusto
authors.initials: A
authors.lastname: Valderrama
authors.forename: I King
authors.initials: IK
authors.lastname: Jordan
authors.forename: Victoria V
authors.initials: VV
authors.lastname: Lunyak
mesh_terms: D000595:Amino Acid Sequence; D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D015153:Blotting, Western; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage / Q000235:genetics*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D013058:Mass Spectrometry / Q000379:methods; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
chemical_list: D000903:Antibiotics, Antineoplastic; D002843:Chromatin; D006657:Histones; D001761:Bleomycin