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Cited by 5Microtubule and mitosis dynamicsDNA Repair MechanismsGenomics and Chromatin Dynamics

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Centromere protection requires strict mitotic inactivation of the Bloom syndrome helicase complex

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Fernández-Casañas, María, Karanika, Eleftheria, Aliyaskarova, Umit, Olukoga, Tomisin, Herbert, Alex D., Oliver, Antony W., Day, Matthew, Crncec, Adrijana, Chan, Kok-Lung·2025·Nature Communications
DOI 10.1038/s41467-025-62966-6PMC PMC12373852

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Abstract

The BTRR ( B LM/ T OP3A/ R MI1/ R MI2) complex resolves DNA replication and recombination intermediates to maintain genome stability. Alongside PICH, they target mitotic DNA intertwinements, known as ultrafine DNA bridges, facilitating chromosome segregation. Both BLM and PICH undergo transient mitotic hyper-phosphorylation, but the biological significance of this remains elusive. Here, we uncover that during early mitosis, CDK1 and PLK1 constrain BTRR complex activities at centromeres. CDK1 destabilises the complex, limiting its binding to PICH at specialised chromatin underneath kinetochores. Inactivating the BLM-TOP3A interaction compromises the UFB-binding complex functions and prevents centromere destruction. Different phosphorylation on BLM affects the TRR subcomplex interaction and the mitotic activity, particularly phosphorylation at Ser144 and multiple PLK1-target sites suppresses illegitimate centromeric DNA unwinding. However, unleashing such activity after sister-chromatid cohesion inactivation facilitates the separation of entangled chromosomes. Here, we show a centromere protection pathway in human mitotic cells, heavily reliant on a tight spatiotemporal control of the BTRR complex.

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Metadata

Authors
Fernández-Casañas, M., Karanika, E., Aliyaskarova, U., Olukoga, T., Herbert, A. D., Oliver, A. W., Day, M., Crncec, A., & Chan, K.-L.
Affiliations
  • Institute of Cancer Research (GB)
  • University of Sussex (GB)
  • Queen Mary University of London (GB)
Corresponding author
Chan, Kok-Lung
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2025-08-22
Volume
16
Issue
1
Pages
7832-7832
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-025-62966-6
PMC
PMC12373852
OpenAlex
W4413421358
Cited by
5
References
2
Citations by year
2026: 5
FWCI
2.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Wellcome Trust (225348/Z/22/Z, 104178/Z/14/A)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
Bloom syndrome helicase, BLM, TOP3A, RMI1, RMI2, PICH, CDK1, PLK1, sister chromatid cohesion, chromosome segregation, genome stability
MeSH terms
Polo-Like Kinase 1, Centromere, DNA-Binding Proteins, HeLa Cells, Humans, Mitosis, Nuclear Proteins, Phosphorylation, Proto-Oncogene Proteins, CDC2 Protein Kinase, Protein Serine-Threonine Kinases, Kinetochores, Cell Cycle Proteins, Chromosome Segregation, Multiprotein Complexes, RecQ Helicases

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