Direct non transcriptional role of NF-Y in DNA replication

Benatti, Paolo, Belluti, Silvia, Miotto, Benoit, Neusiedler, Julia, Dolfini, Diletta, Drac, Marjorie, Basile, Valentina, Schwob, Etienne, Mantovani, Roberto, Blow, J. Julian and Imbriano, Carol (2016) Direct non transcriptional role of NF-Y in DNA replication. Biochimica Et Biophysica Acta-Molecular Cell Research, 1863 (4). pp. 673-685. ISSN 0167-4889

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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.

Item Type: Article
Uncontrolled Keywords: ccaat-binding factor,dna replication,nf-y,transcription factors,xenopus cell-free system
Faculty \ School:
Depositing User: LivePure Connector
Date Deposited: 10 Jun 2024 15:31
Last Modified: 16 Jul 2024 01:40
DOI: 10.1016/j.bbamcr.2015.12.019

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