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The replication initiation determinant protein (RepID) modulates replication by recruiting CUL4 to chromatin

Author

Listed:
  • Sang-Min Jang

    (Center for Cancer Research, NCI, NIH)

  • Ya Zhang

    (Center for Cancer Research, NCI, NIH)

  • Koichi Utani

    (Center for Cancer Research, NCI, NIH)

  • Haiqing Fu

    (Center for Cancer Research, NCI, NIH)

  • Christophe E. Redon

    (Center for Cancer Research, NCI, NIH)

  • Anna B. Marks

    (Center for Cancer Research, NCI, NIH)

  • Owen K. Smith

    (Center for Cancer Research, NCI, NIH)

  • Catherine J. Redmond

    (Center for Cancer Research, NCI, NIH)

  • Adrian M. Baris

    (Center for Cancer Research, NCI, NIH)

  • Danielle A. Tulchinsky

    (Center for Cancer Research, NCI, NIH)

  • Mirit I. Aladjem

    (Center for Cancer Research, NCI, NIH)

Abstract

Cell cycle progression in mammals is modulated by two ubiquitin ligase complexes, CRL4 and SCF, which facilitate degradation of chromatin substrates involved in the regulation of DNA replication. One member of the CRL4 complex, the WD-40 containing protein RepID (DCAF14/PHIP), selectively binds and activates a group of replication origins. Here we show that RepID recruits the CRL4 complex to chromatin prior to DNA synthesis, thus playing a crucial architectural role in the proper licensing of chromosomes for replication. In the absence of RepID, cells rely on the alternative ubiquitin ligase, SKP2-containing SCF, to progress through the cell cycle. RepID depletion markedly increases cellular sensitivity to SKP2 inhibitors, which triggered massive genome re-replication. Both RepID and SKP2 interact with distinct, non-overlapping groups of replication origins, suggesting that selective interactions of replication origins with specific CRL components execute the DNA replication program and maintain genomic stability by preventing re-initiation of DNA replication.

Suggested Citation

  • Sang-Min Jang & Ya Zhang & Koichi Utani & Haiqing Fu & Christophe E. Redon & Anna B. Marks & Owen K. Smith & Catherine J. Redmond & Adrian M. Baris & Danielle A. Tulchinsky & Mirit I. Aladjem, 2018. "The replication initiation determinant protein (RepID) modulates replication by recruiting CUL4 to chromatin," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05177-6
    DOI: 10.1038/s41467-018-05177-6
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    Cited by:

    1. Xiaohua Xu & Chou-Wei Chang & Min Li & Kenneth Omabe & Nhung Le & Yi-Hsuan Chen & Feng Liang & Yilun Liu, 2023. "DNA replication initiation factor RECQ4 possesses a role in antagonizing DNA replication initiation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Karl-Uwe Reusswig & Julia Bittmann & Martina Peritore & Mathilde Courtes & Benjamin Pardo & Michael Wierer & Matthias Mann & Boris Pfander, 2022. "Unscheduled DNA replication in G1 causes genome instability and damage signatures indicative of replication collisions," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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