Direct non transcriptional role of NF-Y in DNA replication

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.
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Paolo Benatti, Silvia Belluti, Benoit Miotto, Julia Neusiedler, Diletta Dolfini, et al.. Direct non transcriptional role of NF-Y in DNA replication. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2016, 1863 (4), pp.673-685. ⟨10.1016/j.bbamcr.2015.12.019⟩. ⟨inserm-02132560⟩

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