Dbf4-dependent kinase finetunes Ino80 function at chromosome replication origins
The highly conserved Dbf4-Dependent Kinase (DDK) plays a pivotal role during S phase. It phosphorylates the replicative helicase (minichromosome maintenance, MCM complex), which leads to the initiation of replication. However, few other targets, besides the MCM complex, are known, leaving DDK an understudied kinase. Here, we determine the nuclear DDK-dependent phosphoproteome by a two-pronged mass spectrometry approach. Among ~ 400 DDK-dependent phosphorylation targets, we find the Arp8 subunit of the INO80 chromatin remodeling complex. Arp8 phosphorylation stabilises INO80's complex integrity, finetunes its nucleosome spacing at replication origins, stimulates replication and improves the replication stress response. Taken together, we report the regulation of a chromatin remodeler with nucleosome-spacing activity by the cell-cycle machinery. DDK not only regulates the core replication machinery but also regulates a factor that generates replication-conducive chromatin architecture at replication origins.
Authors
- Boris Pfander (ORCID: https://orcid.org/0000-0003-2180-5054)
- Lorenzo Galanti (ORCID: https://orcid.org/0000-0003-2538-3581)
- Johannes Stigler (ORCID: https://orcid.org/0000-0003-2472-5332)
- Christoph F. Kurat (ORCID: https://orcid.org/0000-0003-0962-3258)
- Erika Chacin (ORCID: https://orcid.org/0000-0001-5872-3744)
- Priyanka Bansal (ORCID: https://orcid.org/0000-0002-8276-5466)
- Chandni Kumar (ORCID: https://orcid.org/0000-0002-7872-9251)
- Shibojyoti Lahiri (ORCID: https://orcid.org/0000-0002-2018-9870)
- Tobias Straub (ORCID: https://orcid.org/0000-0002-0547-0453)
- Petra Vizjak (ORCID: https://orcid.org/0009-0009-4528-6499)
- Philipp Korber (ORCID: https://orcid.org/0000-0001-7526-6549)
- Garp Linder
- A. Imhof
- Marisa Müller (ORCID: https://orcid.org/0000-0002-5037-8154)
- Jessica Furtmeier
- Lorenz Spechtenhauser
- Felix Mueller-Planitz
- Belen Gómez-González
- María Ángeles Ortíz-Bazán
- Andrés Aguilera
- Juan de Dios Barba Tena (ORCID: https://orcid.org/0000-0002-3562-8071)
Institutions
- Boehringer Ingelheim (Germany) (DE)
- TU Dortmund University (DE)
- The Francis Crick Institute (GB)
- Bayreuth Medical Center (DE)
- Centro Andaluz de Biología Molecular y Medicina Regenerativa (ES)
- University Hospital Carl Gustav Carus (DE)
- University of Bayreuth (DE)
- Bayer (Germany) (DE)
- Technische Universität Dresden (DE)
- Universidad de Sevilla (ES)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-03-28
- DOI
- https://doi.org/10.1038/s41467-026-70698-4
- Primary Topic
- DNA Repair Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00