DNA binding protein
; DNA binding protein sap1
; protein
; shelterin protein
; single stranded DNA
; taz1 protein
; unclassified drug
; DNA binding protein
; Sap1 protein, S pombe
; Schizosaccharomyces pombe protein
; single stranded DNA
; Article
; cell mutant
; cell nucleus membrane
; cell stress
; cellular distribution
; controlled study
; DNA damage checkpoint
; DNA replication
; DNA replication origin
; fission yeast
; gene interaction
; gene rearrangement
; genome analysis
; genomic instability
; priority journal
; protein interaction
; DNA damage
; fungal genome
; genomic instability
; metabolism
; mutation
; physiology
; Schizosaccharomyces
; DNA Damage
; DNA Replication
; DNA, Single-Stranded
; DNA-Binding Proteins
; Gene Rearrangement
; Genome, Fungal
; Genomic Instability
; Mutation
; Replication Origin
; Schizosaccharomyces
; Schizosaccharomyces pombe Proteins
英文摘要:
The dynamic nature of genome organization impacts critical nuclear functions including the regulation of gene expression, replication, and DNA damage repair. Despite significant progress, the mechanisms responsible for reorganization of the genome in response to cellular stress, such as aberrant DNA replication, are poorly understood. Here, we show that fission yeast cells carrying a mutation in the DNA-binding protein Sap1 show defects in DNA replication progression and genome stability and display extensive changes in genome organization. Chromosomal regions such as subtelomeres that show defects in replication progression associate with the nuclear envelope in sap1 mutant cells. Moreover, highresolution, genome-wide chromosome conformation capture (Hi-C) analysis revealed prominent contacts between telomeres and chromosomal arm regions containing replication origins proximal to binding sites for Taz1, a component of the Shelterin telomere protection complex. Strikingly, we find that Shelterin components are required for interactions between Taz1-associated chromosomal arm regions and telomeres. These analyses reveal an unexpected role for Shelterin components in genome reorganization in cells experiencing replication stress, with important implications for understanding the mechanisms governing replication and genome stability.
Mizuguchi, T., Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States, Department of Human Genetics, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan; Taneja, N., Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States; Matsuda, E., Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States; Belton, J.-M., Howard Hughes Medical Institute, Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, United States; FitzGerald, P., Genome Analysis Unit, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States; Dekker, J., Howard Hughes Medical Institute, Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, United States; Grewal, S.I.S., Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States
Recommended Citation:
Mizuguchi T.,Taneja N.,Matsuda E.,et al. Shelterin components mediate genome reorganization in response to replication stress[J]. Proceedings of the National Academy of Sciences of the United States of America,2017-01-01,114(21)