Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation
Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation
复制标题
组蛋白 H3 Lys 27 单甲基化缺陷的四膜虫突变体复制伸长受损
DOI：
10.1101/gad.218966.113
复制
发表时间：
2013-08-01
影响因子：
10.5
通讯作者：
Liu, Yifan
中科院分区：
文献类型：
--
作者：
Gao, Shan;Xiong, Jie;Liu, Yifan
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.
