Abstract
MORF4-related gene on chromosome 15 (MRG15) is a core component of the NuA4/Tip60 histone acetyltransferase complex that modifies chromatin structure. We here demonstrate that Mrg15 null and heterozygous mouse embryonic fibroblasts exhibit an impaired DNA-damage response post gamma irradiation, when compared to wild-type cells. Defects in DNA-repair and cell growth, and delayed recruitment of repair proteins to sites of damage were observed. Formation of phosphorylated H2AX and 53BP1 foci was delayed in Mrg15 mutant versus wild-type cells following irradiation. These data implicate a novel role for MRG15 in DNA-damage repair in mammalian cells.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Animals
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Apoptosis / radiation effects
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Cell Nucleus / metabolism
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Cell Proliferation / radiation effects
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Cells, Cultured
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Chromosomal Proteins, Non-Histone / deficiency*
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Chromosomal Proteins, Non-Histone / genetics*
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Chromosomal Proteins, Non-Histone / metabolism
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DNA Damage
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DNA Repair*
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DNA-Binding Proteins
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Embryonic Stem Cells / cytology
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Embryonic Stem Cells / metabolism*
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Embryonic Stem Cells / radiation effects*
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Fibroblasts / cytology
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Fibroblasts / metabolism*
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Fibroblasts / radiation effects*
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Gamma Rays / adverse effects
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Gene Deletion
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Heterozygote
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Histones / metabolism
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Intracellular Signaling Peptides and Proteins / metabolism
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Mice
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Phosphoproteins / metabolism
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Trans-Activators / deficiency*
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Trans-Activators / genetics*
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Trans-Activators / metabolism
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Tumor Suppressor p53-Binding Protein 1
Substances
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Chromosomal Proteins, Non-Histone
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DNA-Binding Proteins
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H2AX protein, mouse
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Histones
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Intracellular Signaling Peptides and Proteins
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MRG15 protein, mouse
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Phosphoproteins
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Trans-Activators
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Trp53bp1 protein, mouse
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Tumor Suppressor p53-Binding Protein 1