5-Hydroxymethylcytosine Marks Sites of DNA Damage and Promotes Genome Stability

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 fo...

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Main Authors: Georgia Rose Kafer, Xuan Li, Takuro Horii, Isao Suetake, Shoji Tajima, Izuho Hatada, Peter Mark Carlton
Format: Article
Language:English
Published: Elsevier 2016-02-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124716000565
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author Georgia Rose Kafer
Xuan Li
Takuro Horii
Isao Suetake
Shoji Tajima
Izuho Hatada
Peter Mark Carlton
author_facet Georgia Rose Kafer
Xuan Li
Takuro Horii
Isao Suetake
Shoji Tajima
Izuho Hatada
Peter Mark Carlton
author_sort Georgia Rose Kafer
collection DOAJ
description 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.
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spelling doaj.art-86e8dff51c0c44bab7e73c018cad286c2022-12-22T01:45:49ZengElsevierCell Reports2211-12472016-02-011461283129210.1016/j.celrep.2016.01.0355-Hydroxymethylcytosine Marks Sites of DNA Damage and Promotes Genome StabilityGeorgia Rose Kafer0Xuan Li1Takuro Horii2Isao Suetake3Shoji Tajima4Izuho Hatada5Peter Mark Carlton6Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto 606-8501, JapanInstitute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto 606-8501, JapanLaboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8511, JapanLaboratory of Epigenetics, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, JapanLaboratory of Epigenetics, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, JapanLaboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8511, JapanInstitute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto 606-8501, Japan5-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.http://www.sciencedirect.com/science/article/pii/S2211124716000565
spellingShingle Georgia Rose Kafer
Xuan Li
Takuro Horii
Isao Suetake
Shoji Tajima
Izuho Hatada
Peter Mark Carlton
5-Hydroxymethylcytosine Marks Sites of DNA Damage and Promotes Genome Stability
Cell Reports
title 5-Hydroxymethylcytosine Marks Sites of DNA Damage and Promotes Genome Stability
title_full 5-Hydroxymethylcytosine Marks Sites of DNA Damage and Promotes Genome Stability
title_fullStr 5-Hydroxymethylcytosine Marks Sites of DNA Damage and Promotes Genome Stability
title_full_unstemmed 5-Hydroxymethylcytosine Marks Sites of DNA Damage and Promotes Genome Stability
title_short 5-Hydroxymethylcytosine Marks Sites of DNA Damage and Promotes Genome Stability
title_sort 5 hydroxymethylcytosine marks sites of dna damage and promotes genome stability
url http://www.sciencedirect.com/science/article/pii/S2211124716000565
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