The heterotrimeric transcription factor NF-Y plays a pioneer role in the transcriptional control of promoters containing the CCAAT-box, among which genes involved in cell cycle regulation. The expression levels of the sequence specific subunit NF-YA increase at the onset of S phase, and NF-YA loss in primary and tumor mammalian cells triggers defects in S-phase progression. Here, we show 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 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. Using a Xenopus cell-free system, we unambiguously demonstrate a direct non-transcriptional role of NF-Y in the overall efficiency of DNA replication. Spontaneous DNA damage occurs in NF-YA-deficient cells, while NF-YA overexpression reduces the sensitivity to replication stress, suggesting a role for NF-Y in replication stress response and genome maintenance. Our findings broaden the activity of NF-Y on a DNA metabolism other than transcription, supporting the existence of specific transcription factors required for proper and efficient DNA replication.

Direct non transcriptional role of the CCAAT-factor NF-Y in DNA replication / Belluti, Silvia; Benatti, Paolo; Benoit, Miotto; Julia, Neusiedler; Diletta, Dolfini; Marjorie, Drac; Etienne, Schwob; Roberto, Mantovani; Julian Blow, J.; Imbriano, Carol. - (2016). ((Intervento presentato al convegno At the Intersection of DNA Replication and Genome Maintenance: from Mechanisms to Therapy tenutosi a Trieste nel 27/06/2016.

Direct non transcriptional role of the CCAAT-factor NF-Y in DNA replication

BELLUTI, SILVIA;BENATTI, Paolo;IMBRIANO, Carol
2016

Abstract

The heterotrimeric transcription factor NF-Y plays a pioneer role in the transcriptional control of promoters containing the CCAAT-box, among which genes involved in cell cycle regulation. The expression levels of the sequence specific subunit NF-YA increase at the onset of S phase, and NF-YA loss in primary and tumor mammalian cells triggers defects in S-phase progression. Here, we show 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 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. Using a Xenopus cell-free system, we unambiguously demonstrate a direct non-transcriptional role of NF-Y in the overall efficiency of DNA replication. Spontaneous DNA damage occurs in NF-YA-deficient cells, while NF-YA overexpression reduces the sensitivity to replication stress, suggesting a role for NF-Y in replication stress response and genome maintenance. Our findings broaden the activity of NF-Y on a DNA metabolism other than transcription, supporting the existence of specific transcription factors required for proper and efficient DNA replication.
At the Intersection of DNA Replication and Genome Maintenance: from Mechanisms to Therapy
Trieste
27/06/2016
Belluti, Silvia; Benatti, Paolo; Benoit, Miotto; Julia, Neusiedler; Diletta, Dolfini; Marjorie, Drac; Etienne, Schwob; Roberto, Mantovani; Julian Blow, J.; Imbriano, Carol
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1107133
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