title: 5-Hydroxymethylcytosine Marks Sites of DNA Damage and Promotes Genome Stability.
abstract: 5-hydroxymethylcytosine (5hmC) is a DNA base created during active DNA demethylation by the recently discovered TET enzymes. 5hmC has essential roles in gene expression and differentiation. Here, we demonstrate that 5hmC also localizes to sites of DNA damage and repair. 5hmC accumulates at damage foci induced by aphidicolin and microirradiation and colocalizes with major DNA damage response proteins 53BP1 and γH2AX, revealing 5hmC as an epigenetic marker of DNA damage. Deficiency for the TET enzymes eliminates damage-induced 5hmC accumulation and elicits chromosome segregation defects in response to replication stress. Our results indicate that the TET enzymes and 5hmC play essential roles in ensuring genome integrity.
authors: Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto 606-8501, Japan; CREST, Japan Science and Technology Agency.
authors: Georgia Rose
authors: GR
authors: Kafer
authors: Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto 606-8501, Japan.
authors: Xuan
authors: X
authors: Li
authors: Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8511, Japan.
authors: Takuro
authors: T
authors: Horii
authors: Laboratory of Epigenetics, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan; CREST, Japan Science and Technology Agency.
authors: Isao
authors: I
authors: Suetake
authors: Laboratory of Epigenetics, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
authors: Shoji
authors: S
authors: Tajima
authors: Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8511, Japan.
authors: Izuho
authors: I
authors: Hatada
authors: Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto 606-8501, Japan; CREST, Japan Science and Technology Agency. Electronic address: pcarlton@icems.kyoto-u.ac.jp.
authors: Peter Mark
authors: PM
authors: Carlton
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D064113:CRISPR-Cas Systems; D002460:Cell Line; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004249:DNA Damage; D019175:DNA Methylation; D004260:DNA Repair; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D049308:Dioxygenases; D044127:Epigenesis, Genetic; D016678:Genome; D042822:Genomic Instability; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D000071857:Tumor Suppressor p53-Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D011518:Proto-Oncogene Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; C011865:5-hydroxymethylcytosine; D016590:Aphidicolin; D044503:5-Methylcytosine; D003596:Cytosine; D049308:Dioxygenases; C541081:TET2 protein, human; C495153:RAD51 protein, human; D051135:Rad51 Recombinase