Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion

Giuseppe Cortone, Ge Zheng, Pasquale Pensieri, Viviana Chiappetta, Rosarita Tatè, Eva Malacaria, Pietro Pichierri, Hongtao Yu, Francesca M. Pisani

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)e1007622
JournalPLoS Genetics
Volume14
Issue number10
DOIs
StatePublished - Oct 1 2018

Fingerprint

DNA helicases
DNA Helicases
Chromatids
chromatids
breakage
cohesion
DNA Replication
DNA replication
DNA
Interphase
Mitosis
Chromatin
Fluorescent Antibody Technique
interphase
mitosis
fluorescent antibody technique
chromatin
Peptides
peptide
peptides

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion. / Cortone, Giuseppe; Zheng, Ge; Pensieri, Pasquale; Chiappetta, Viviana; Tatè, Rosarita; Malacaria, Eva; Pichierri, Pietro; Yu, Hongtao; Pisani, Francesca M.

In: PLoS Genetics, Vol. 14, No. 10, 01.10.2018, p. e1007622.

Research output: Contribution to journalArticle

Cortone, G, Zheng, G, Pensieri, P, Chiappetta, V, Tatè, R, Malacaria, E, Pichierri, P, Yu, H & Pisani, FM 2018, 'Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion', PLoS Genetics, vol. 14, no. 10, pp. e1007622. https://doi.org/10.1371/journal.pgen.1007622
Cortone, Giuseppe ; Zheng, Ge ; Pensieri, Pasquale ; Chiappetta, Viviana ; Tatè, Rosarita ; Malacaria, Eva ; Pichierri, Pietro ; Yu, Hongtao ; Pisani, Francesca M. / Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion. In: PLoS Genetics. 2018 ; Vol. 14, No. 10. pp. e1007622.
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