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
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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