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E2F-dependent transcription determines replication capacity and S phase length

Author

Listed:
  • Betheney R. Pennycook

    (University College London
    MRC London Institute of Medical Science Hammersmith Hospital Campus)

  • Eva Vesela

    (University College London)

  • Silvia Peripolli

    (University College London)

  • Tanya Singh

    (University College London)

  • Alexis R. Barr

    (MRC London Institute of Medical Science Hammersmith Hospital Campus
    Imperial College London)

  • Cosetta Bertoli

    (University College London)

  • Robertus A. M. de Bruin

    (University College London
    University College London)

Abstract

DNA replication timing is tightly regulated during S-phase. S-phase length is determined by DNA synthesis rate, which depends on the number of active replication forks and their velocity. Here, we show that E2F-dependent transcription, through E2F6, determines the replication capacity of a cell, defined as the maximal amount of DNA a cell can synthesise per unit time during S-phase. Increasing or decreasing E2F-dependent transcription during S-phase increases or decreases replication capacity, and thereby replication rates, thus shortening or lengthening S-phase, respectively. The changes in replication rate occur mainly through changes in fork speed without affecting the number of active forks. An increase in fork speed does not induce replication stress directly, but increases DNA damage over time causing cell cycle arrest. Thus, E2F-dependent transcription determines the DNA replication capacity of a cell, which affects the replication rate, controlling the time it takes to duplicate the genome and complete S-phase.

Suggested Citation

  • Betheney R. Pennycook & Eva Vesela & Silvia Peripolli & Tanya Singh & Alexis R. Barr & Cosetta Bertoli & Robertus A. M. de Bruin, 2020. "E2F-dependent transcription determines replication capacity and S phase length," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17146-z
    DOI: 10.1038/s41467-020-17146-z
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    Cited by:

    1. Silvia Peripolli & Leticia Meneguello & Chiara Perrod & Tanya Singh & Harshil Patel & Sazia T. Rahman & Koshiro Kiso & Peter Thorpe & Vincenzo Calvanese & Cosetta Bertoli & Robertus A. M. de Bruin, 2024. "Oncogenic c-Myc induces replication stress by increasing cohesins chromatin occupancy in a CTCF-dependent manner," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Jason P. Wray & Elitza M. Deltcheva & Charlotta Boiers & Simon Е Richardson & Jyoti Bikram Chhetri & John Brown & Sladjana Gagrica & Yanping Guo & Anuradha Illendula & Joost H. A. Martens & Hendrik G., 2022. "Regulome analysis in B-acute lymphoblastic leukemia exposes Core Binding Factor addiction as a therapeutic vulnerability," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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