Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation. uri icon

abstract

  • 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 TXR1 cells. TXR1 cells showed a deficiency in histone H3 Lys 27 monomethylation (H3K27me1), while 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 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.

published proceedings

  • Genes Dev

altmetric score

  • 0.75

author list (cited authors)

  • Gao, S., Xiong, J., Zhang, C., Berquist, B. R., Yang, R., Zhao, M., ... Liu, Y.

citation count

  • 53

complete list of authors

  • 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

publication date

  • August 2013