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The COMPASS subunit Spp1 protects nascent DNA at the Tus/Ter replication fork barrier by limiting DNA availability to nucleases

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  • Nagham Ghaddar

    (UM105 Aix-Marseille University, Institute Paoli-Calmettes, Ligue Nationale Contre le Cancer (Equipe Labellisée))

  • Yves Corda

    (UM105 Aix-Marseille University, Institute Paoli-Calmettes, Ligue Nationale Contre le Cancer (Equipe Labellisée))

  • Pierre Luciano

    (UM105 Aix-Marseille University, Institute Paoli-Calmettes, Ligue Nationale Contre le Cancer (Equipe Labellisée))

  • Martina Galli

    (IFOM ETS - the AIRC Institute of Molecular Oncology)

  • Ylli Doksani

    (IFOM ETS - the AIRC Institute of Molecular Oncology)

  • Vincent Géli

    (UM105 Aix-Marseille University, Institute Paoli-Calmettes, Ligue Nationale Contre le Cancer (Equipe Labellisée))

Abstract

Homologous recombination factors play a crucial role in protecting nascent DNA during DNA replication, but the role of chromatin in this process is largely unknown. Here, we used the bacterial Tus/Ter barrier known to induce a site-specific replication fork stalling in S. cerevisiae. We report that the Set1C subunit Spp1 is recruited behind the stalled replication fork independently of its interaction with Set1. Spp1 chromatin recruitment depends on the interaction of its PHD domain with H3K4me3 parental histones deposited behind the stalled fork. Its recruitment prevents the accumulation of ssDNA at the stalled fork by restricting the access of Exo1. We further show that deleting SPP1 increases the mutation rate upstream of the barrier favoring the accumulation of microdeletions. Finally, we report that Spp1 protects nascent DNA at the Tus/Ter stalled replication fork. We propose that Spp1 limits the remodeling of the fork, which ultimately limits nascent DNA availability to nucleases.

Suggested Citation

  • Nagham Ghaddar & Yves Corda & Pierre Luciano & Martina Galli & Ylli Doksani & Vincent Géli, 2023. "The COMPASS subunit Spp1 protects nascent DNA at the Tus/Ter replication fork barrier by limiting DNA availability to nucleases," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41100-4
    DOI: 10.1038/s41467-023-41100-4
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    References listed on IDEAS

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    1. Nicholas A. Willis & Gurushankar Chandramouly & Bin Huang & Amy Kwok & Cindy Follonier & Chuxia Deng & Ralph Scully, 2014. "BRCA1 controls homologous recombination at Tus/Ter-stalled mammalian replication forks," Nature, Nature, vol. 510(7506), pages 556-559, June.
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    5. Arnab Ray Chaudhuri & Elsa Callen & Xia Ding & Ewa Gogola & Alexandra A. Duarte & Ji-Eun Lee & Nancy Wong & Vanessa Lafarga & Jennifer A. Calvo & Nicholas J. Panzarino & Sam John & Amanda Day & Anna V, 2016. "Replication fork stability confers chemoresistance in BRCA-deficient cells," Nature, Nature, vol. 535(7612), pages 382-387, July.
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