Cyclin E/CDK2 and feedback from soluble histone protein regulate the S phase burst of histone biosynthesisCyclin E/CDK2 and feedback from soluble histone protein regulate the S phase burst of histone biosynthesis

Description

Faithful DNA replication requires that cells fine-tune their histone pool in coordination with cell-cycle progression. Replication-dependent histone biosynthesis is initiated at a low level upon cell-cycle commitment, followed by a burst at the G1/S transition, but it remains unclear how exactly the cell regulates this change in histone biosynthesis as DNA replication begins. Here, we use single-cell timelapse imaging to elucidate the mechanisms by which cells modulate histone production during different phases of the cell cycle. We find that CDK2-mediated phosphorylation of NPAT at the Restriction Point triggers histone transcription, which results in a burst of histone mRNA precisely at the G1/S phase boundary. Excess soluble histone protein further modulates histone abundance by promoting the degradation of histone mRNA for the duration of S phase. Thus, cells regulate their histone production in strict coordination with cell-cycle progression by two distinct mechanisms acting in concert. Due to size limitations, representative raw images for main text figures have been included with all raw images available upon request.

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Funders

• American Cancer Society

  United States

  Grant ID: RSG-18-008-01
• Pew Charitable Trusts

  United States

  Grant ID: NA
• National Cancer Institute

  Grant ID: 1DP2CA238330-01
• NIH

  Grant ID: GM065103-16
• NIST-CU

  Grant ID: 70NANB15H226
• NIH

  Grant ID: 1S10RR026680-01A1

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