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题名: Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation
作者: Gao, Shan1; Xiong, Jie2, 3; Zhang, Chunchao4; Berquist, Brian R.5; Yang, Rendong6; Zhao, Meng6; Molascon, Anthony J.1; Kwiatkowski, Shaina Y.1; Yuan, Dongxia2; Qin, Zhaohui6, 7; Wen, Jianfan3; Kapler, Geoffrey M.5; Andrews, Philip C.4, 8, 9; Miao, Wei2; Liu, Yifan1
通讯作者: Miao, W (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China.
关键词: histone methyltransferase ; H3 Lys 27 methylation ; replication stress ; replication elongation ; ssDNA ; replication origin
刊名: GENES & DEVELOPMENT
发表日期: 2013-08-01
DOI: 10.1101/gad.218966.113
卷: 27, 期:15, 页:1662-1679
收录类别: SCI
文章类型: Article
部门归属: [Gao, Shan ; Molascon, Anthony J. ; Kwiatkowski, Shaina Y. ; Liu, Yifan] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA ; [Xiong, Jie ; Yuan, Dongxia ; Miao, Wei] Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China ; [Xiong, Jie ; Wen, Jianfan] Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Wuhan 430072, Peoples R China ; [Zhang, Chunchao ; Andrews, Philip C.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA ; [Berquist, Brian R. ; Kapler, Geoffrey M.] Texas A&M Hlth Sci Ctr, Coll Med, Dept Mol & Cellular Med, College Stn, TX 77843 USA ; [Yang, Rendong ; Zhao, Meng ; Qin, Zhaohui] Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA ; [Qin, Zhaohui] Emory Univ, Ctr Comprehens Informat, Atlanta, GA 30322 USA ; [Andrews, Philip C.] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA ; [Andrews, Philip C.] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: NIH [R01-GM087343, 1P41RR018627, R01-GM53572, R01-HG005119]; National Natural Science Foundation of China [31071993]; Fund of State Key Laboratory of Genetics Resources and Evolution [GREKF10-09]; University of Michigan Rackham Graduate Student Research Grant
类目[WOS]: Cell Biology ; Developmental Biology ; Genetics & Heredity
研究领域[WOS]: Cell Biology ; Developmental Biology ; Genetics & Heredity
摘要: Replication of nuclear DNA occurs in the context of chromatin and is influenced by histone modifications. In the ciliate Tetrahymena thermophila, we identified TXR1, encoding a histone methyltransferase. TXR1 deletion resulted in severe DNA replication stress, manifested by the accumulation of ssDNA, production of aberrant replication intermediates, and activation of robust DNA damage responses. Paired-end Illumina sequencing of ssDNA revealed intergenic regions, including replication origins, as hot spots for replication stress in Delta TXR1 cells. Delta TXR1 cells showed a deficiency in histone H3 Lys 27 monomethylation (H3K27me1), while Delta EZL2 cells, deleting a Drosophila E(z) homolog, were deficient in H3K27 di- and trimethylation, with no detectable replication stress. A point mutation in histone H3 at Lys 27 (H3 K27Q) mirrored the phenotype of Delta TXR1, corroborating H3K27me1 as a key player in DNA replication. Additionally, we demonstrated interactions between TXR1 and proliferating cell nuclear antigen (PCNA). These findings support a conserved pathway through which H3K27me1 facilitates replication elongation.
英文摘要: Replication of nuclear DNA occurs in the context of chromatin and is influenced by histone modifications. In the ciliate Tetrahymena thermophila, we identified TXR1, encoding a histone methyltransferase. TXR1 deletion resulted in severe DNA replication stress, manifested by the accumulation of ssDNA, production of aberrant replication intermediates, and activation of robust DNA damage responses. Paired-end Illumina sequencing of ssDNA revealed intergenic regions, including replication origins, as hot spots for replication stress in Delta TXR1 cells. Delta TXR1 cells showed a deficiency in histone H3 Lys 27 monomethylation (H3K27me1), while Delta EZL2 cells, deleting a Drosophila E(z) homolog, were deficient in H3K27 di- and trimethylation, with no detectable replication stress. A point mutation in histone H3 at Lys 27 (H3 K27Q) mirrored the phenotype of Delta TXR1, corroborating H3K27me1 as a key player in DNA replication. Additionally, we demonstrated interactions between TXR1 and proliferating cell nuclear antigen (PCNA). These findings support a conserved pathway through which H3K27me1 facilitates replication elongation.
关键词[WOS]: RIBOSOMAL-RNA GENES ; EUKARYOTIC DNA-REPLICATION ; NUCLEAR ANTIGEN PCNA ; SINGLE-STRANDED-DNA ; S-PHASE CHECKPOINT ; CHROMATIN-STRUCTURE ; CELL-CYCLE ; HETEROCHROMATIN FORMATION ; GENOME STABILITY ; DAMAGE RESPONSE
语种: 英语
WOS记录号: WOS:000322716000005
ISSN号: 0890-9369
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/19611
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

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作者单位: 1.Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA
2.Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China
3.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Wuhan 430072, Peoples R China
4.Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA
5.Texas A&M Hlth Sci Ctr, Coll Med, Dept Mol & Cellular Med, College Stn, TX 77843 USA
6.Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA
7.Emory Univ, Ctr Comprehens Informat, Atlanta, GA 30322 USA
8.Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA
9.Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA

Recommended Citation:
Gao, Shan; Xiong, Jie; Zhang, Chunchao; Berquist, Brian R.; Yang, Rendong; Zhao, Meng; Molascon, Anthony J.; Kwiatkowski, Shaina Y.; Yuan, Dongxia; Qin, Zhaohui; Wen, Jianfan; Kapler, Geoffrey M.; Andrews, Philip C.; Miao, Wei; Liu, Yifan.Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation,GENES & DEVELOPMENT,2013,27(15):1662-1679
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