Cyclin E/CDK2 and feedback from soluble histone protein regulate the S phase burst of histone biosynthesis. Journal Article uri icon



  • 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.

publication date

  • March 18, 2023

has restriction

  • green

Date in CU Experts

  • March 28, 2023 11:53 AM

Full Author List

  • Armstrong C; Passanisi VJ; Ashraf HM; Spencer SL

author count

  • 4

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