Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion
Autor: | Rosarita Tatè, Pasquale Pensieri, Francesca M. Pisani, Viviana Chiappetta, Hongtao Yu, Pietro Pichierri, Ge Zheng, Giuseppe Cortone, Eva Malacaria |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Genome instability Cancer Research Cultured tumor cells Synthesis Phase Cell Cycle Proteins DNA helicases Biochemistry DEAD-box RNA Helicases Database and Informatics Methods 0302 clinical medicine Chromosome Segregation Small interfering RNAs Cell Cycle and Cell Division Genetics (clinical) Chromosome Biology Intracellular Signaling Peptides and Proteins Syndrome Chromatin Cell biology Enzymes Establishment of sister chromatid cohesion Nucleic acids Cell Processes 030220 oncology & carcinogenesis Cell lines Helicases Chromatid biological phenomena cell phenomena and immunity Biological cultures Sequence Analysis Protein Binding Research Article DNA Replication lcsh:QH426-470 Bioinformatics DNA replication sister chromatid cohesion DNA helicase Warsaw breakage syndrome chromosome dynamics Biology Chromatids Genomic Instability Chromosomes Replication fork protection 03 medical and health sciences Sequence Motif Analysis Genetics Humans Abnormalities Multiple HeLa cells Non-coding RNA Molecular Biology Ecology Evolution Behavior and Systematics Cohesin Biology and life sciences Helicase Proteins DNA Cell Biology Cell cultures Gene regulation Research and analysis methods lcsh:Genetics 030104 developmental biology biology.protein Enzymology RNA Gene expression |
Zdroj: | PLoS Genetics PLOS genetics (Online) 14 (2018): e1007622. doi:10.1371/journal.pgen.1007622 info:cnr-pdr/source/autori:Cortone G, Zheng G, Pensieri P, Chiappetta V, Tatè R, Malacaria E, Pichierri P, Yu H, Pisani FM./titolo:Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion./doi:10.1371%2Fjournal.pgen.1007622/rivista:PLOS genetics (Online)/anno:2018/pagina_da:e1007622/pagina_a:/intervallo_pagine:e1007622/volume:14 PLoS Genetics, Vol 14, Iss 10, p e1007622 (2018) |
ISSN: | 1553-7404 |
Popis: | Establishment of sister chromatid cohesion is coupled to DNA replication, but the underlying molecular mechanisms are incompletely understood. DDX11 (also named ChlR1) is a super-family 2 Fe-S cluster-containing DNA helicase implicated in Warsaw breakage syndrome (WABS). Herein, we examined the role of DDX11 in cohesion establishment in human cells. We demonstrated that DDX11 interacts with Timeless, a component of the replication fork-protection complex, through a conserved peptide motif. The DDX11-Timeless interaction is critical for sister chromatid cohesion in interphase and mitosis. Immunofluorescence studies further revealed that cohesin association with chromatin requires DDX11. Finally, we demonstrated that DDX11 localises at nascent DNA by SIRF analysis. Moreover, we found that DDX11 promotes cohesin binding to the DNA replication forks in concert with Timeless and that recombinant purified cohesin interacts with DDX11 in vitro. Collectively, our results establish a critical role for the DDX11-Timeless interaction in coordinating DNA replication with sister chromatid cohesion, and have important implications for understanding the molecular basis of WABS. Author summary Chromosomes are DNA molecules that contain the genetic information. During replication, the two sister DNA molecules covered by proteins (sister chromatids) are held together by many copies of a ring-like protein complex named cohesin, in a process called sister-chromatid cohesion. Before a cell divides, the cohesin rings are removed from the two sister chromatids to allow their migration towards the opposite poles of the dividing mother cell. At the end of this process, the two daughter cells have inherited a complete set of chromosomes. Before the next cell division, chromosomes are duplicated with high speed and fidelity. This important task is performed by the DNA replication machinery, a sophisticated apparatus made of several enzymes and proteins. In the present study, we have demonstrated that DDX11 and Timeless, two subunits of the DNA replication machinery, recruit the cohesin rings to promote their stable binding to the newly duplicated chromosomes, that is the establishment of sister-chromatid cohesion. In human cells that were genetically engineered to reduce the level of DDX11, we observed that sister-chromatid cohesion was loosened and association of cohesin to chromosomes was reduced. Our experimental results contribute to our understanding of the molecular mechanisms underlying the functional coupling between DNA replication and sister-chromatid cohesion in human cells. |
Databáze: | OpenAIRE |
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