Mrg15 null and heterozygous mouse embryonic fibroblasts exhibit DNA-repair defects post exposure to gamma ionizing radiation.
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.
Garcia
Sandra N
SN
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 15535 Lambda Drive, STCBM #3.100, San Antonio, TX 78245, USA.
Kirtane
Bhakti M
BM
Podlutsky
Andrej J
AJ
Pereira-Smith
Olivia M
OM
Tominaga
Kaoru
K
D000107:Acetylation; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000528:radiation effects; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D005720:Gamma Rays / Q000009:adverse effects; D017353:Gene Deletion; D006579:Heterozygote; D006657:Histones / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D000071857:Tumor Suppressor p53-Binding Protein 1
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D000071857:Tumor Suppressor p53-Binding Protein 1; C471162:MRG15 protein, mouse; C498302:Trp53bp1 protein, mouse; C475961:gamma-H2AX protein, mouse