Mrg15 null and heterozygous mouse embryonic fibroblasts exhibit DNA-repair defects post exposure to gamma ionizing radiation

FEBS Lett. 2007 Nov 13;581(27):5275-81. doi: 10.1016/j.febslet.2007.10.017. Epub 2007 Oct 18.

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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Apoptosis / radiation effects
  • Cell Nucleus / metabolism
  • Cell Proliferation / radiation effects
  • Cells, Cultured
  • Chromosomal Proteins, Non-Histone / deficiency*
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA Damage
  • DNA Repair*
  • DNA-Binding Proteins
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Embryonic Stem Cells / radiation effects*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Fibroblasts / radiation effects*
  • Gamma Rays / adverse effects
  • Gene Deletion
  • Heterozygote
  • Histones / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Phosphoproteins / metabolism
  • Trans-Activators / deficiency*
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Tumor Suppressor p53-Binding Protein 1

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • H2AX protein, mouse
  • Histones
  • Intracellular Signaling Peptides and Proteins
  • MRG15 protein, mouse
  • Phosphoproteins
  • Trans-Activators
  • Trp53bp1 protein, mouse
  • Tumor Suppressor p53-Binding Protein 1