Direct non transcriptional role of NF-Y in DNA replication

Paolo Benatti, Silvia Belluti, Benoit Miotto, Julia Neusiedler, Diletta Dolfini, Marjorie Drac, Valentina Basile, Etienne Schwob, Roberto Mantovani, J. Julian Blow, Carol Imbriano (Lead / Corresponding author)

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Abstract

NF-Y is a heterotrimeric transcription factor, which plays a pioneer role in the transcriptional control of promoters containing the CCAAT-box, among which genes involved in cell cycle regulation, apoptosis and DNA damage response. The knock-down of the sequence-specific subunit NF-YA triggers defects in S-phase progression, which lead to apoptotic cell death. Here, we report that NF-Y has a critical function in DNA replication progression, independent from its transcriptional activity. NF-YA colocalizes with early DNA replication factories, its depletion affects the loading of replisome proteins to DNA, among which Cdc45, and delays the passage from early to middle-late S phase. Molecular combing experiments are consistent with a role for NF-Y in the control of fork progression. Finally, we unambiguously demonstrate a direct non-transcriptional role of NF-Y in the overall efficiency of DNA replication, specifically in the DNA elongation process, using a Xenopus cell-free system. Our findings broaden the activity of NF-Y on a DNA metabolism other than transcription, supporting the existence of specific TFs required for proper and efficient DNA replication.

Original languageEnglish
Pages (from-to)673-685
Number of pages13
JournalBiochimica et Biophysica Acta. Molecular Cell Research
Volume1863
Issue number4
Early online date28 Dec 2015
DOIs
Publication statusPublished - 1 Apr 2016

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Keywords

  • CCAAT-binding factor
  • DNA replication
  • NF-Y
  • Transcription factors
  • Xenopus cell-free system

Cite this

Benatti, P., Belluti, S., Miotto, B., Neusiedler, J., Dolfini, D., Drac, M., Basile, V., Schwob, E., Mantovani, R., Blow, J. J., & Imbriano, C. (2016). Direct non transcriptional role of NF-Y in DNA replication. Biochimica et Biophysica Acta. Molecular Cell Research, 1863(4), 673-685. https://doi.org/10.1016/j.bbamcr.2015.12.019