TY - JOUR
T1 - Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation
AU - Gao, Shan
AU - Xiong, Jie
AU - Zhang, Chunchao
AU - Berquist, Brian R.
AU - Yang, Rendong
AU - Zhao, Meng
AU - Molascon, Anthony J.
AU - Kwiatkowski, Shaina Y.
AU - Yuan, Dongxia
AU - Qin, Zhaohui
AU - Wen, Jianfan
AU - Kapler, Geoffrey M.
AU - Andrews, Philip C.
AU - Miao, Wei
AU - Liu, Yifan
PY - 2013/8/1
Y1 - 2013/8/1
N2 - 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 ΔTXR1 cells. ΔTXR1 cells showed a deficiency in histone H3 Lys 27 monomethylation (H3K27me1), while ΔEZL2 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 ΔTXR1, 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.
AB - 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 ΔTXR1 cells. ΔTXR1 cells showed a deficiency in histone H3 Lys 27 monomethylation (H3K27me1), while ΔEZL2 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 ΔTXR1, 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.
KW - H3 Lys 27 methylation
KW - Histone methyltransferase
KW - Replication elongation
KW - Replication origin
KW - Replication stress
KW - ssDNA
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U2 - 10.1101/gad.218966.113
DO - 10.1101/gad.218966.113
M3 - Article
C2 - 23884606
AN - SCOPUS:84881065762
SN - 0890-9369
VL - 27
SP - 1662
EP - 1679
JO - Genes and Development
JF - Genes and Development
IS - 15
ER -