SRBD1, a highly conserved gene required for chromosome individualization
Despite significant progress made in functional genomics, the roles of a relatively small number of essential genes remain enigmatic. Here, we characterize S1 RNA-binding domain-containing protein 1 (SRBD1), an essential gene with no previously assigned function. Through genetic, proteomic, and functional approaches, we discovered that SRBD1 is a DNA-binding protein and a key component of the mitotic chromatid axis. The loss of SRBD1 results in a pronounced defect in sister chromatid segregation that strikingly resembles the phenotype observed when sister chromatid decatenation is perturbed by topoisomerase IIα (TOP2A) dysfunction. Using genetic screens, we uncovered that the requirement for SRBD1 depends on the presence of condensin II but not condensin I. Moreover, we found that SRBD1 activity is most critical during prophase, when chromosome condensation is established. Taking these results together, we propose that SRBD1 acts during prophase to safeguard the decatenation process to prevent the formation of difficult-to-resolve DNA structures, thereby averting severe chromosome missegregations.
Authors
- Wilbert Zwart (ORCID: https://orcid.org/0000-0002-9823-7289)
- Razvan Borza (ORCID: https://orcid.org/0000-0003-2759-9511)
- Anastassis Perrakis (ORCID: https://orcid.org/0000-0002-1151-6227)
- Patrick H. N. Celie (ORCID: https://orcid.org/0000-0002-6557-078X)
- Kees Jalink (ORCID: https://orcid.org/0000-0001-7019-3440)
- Thijn R. Brummelkamp (ORCID: https://orcid.org/0000-0002-3066-7071)
- Jonne A. Raaijmakers (ORCID: https://orcid.org/0000-0003-1759-8347)
- Isabel Mayayo‐Peralta
- Claire Hoencamp (ORCID: https://orcid.org/0000-0003-2047-4724)
- Ahmed M.O. Elbatsh (ORCID: https://orcid.org/0000-0001-8012-3999)
- Nuria Vaquero‐Siguero
- Leila Nahidiazar (ORCID: https://orcid.org/0000-0002-1154-4973)
- Jos Jonkers (ORCID: https://orcid.org/0000-0002-9264-9792)
- Louise M.E. Janssen (ORCID: https://orcid.org/0000-0002-5559-0330)
- Benjamin D. Rowland (ORCID: https://orcid.org/0000-0002-0694-8463)
- Alexander Fish (ORCID: https://orcid.org/0000-0002-4994-1536)
- Onno B. Bleijerveld (ORCID: https://orcid.org/0000-0002-9395-2347)
- Sarah C. Moser (ORCID: https://orcid.org/0000-0002-1678-4079)
- René H. Medema (ORCID: https://orcid.org/0000-0002-6754-0381)
- Liesbeth Hoekman (ORCID: https://orcid.org/0000-0002-3552-6390)
- Abdelghani Mazouzi (ORCID: https://orcid.org/0000-0003-0298-6304)
- Amber Hondema
- Anoek Friskes (ORCID: https://orcid.org/0000-0002-9845-3715)
- Justina Kazokaitė-Adomaitienė
Institutions
- Oncode Institute (NL)
- Princess Máxima Center (NL)
- Cancer Genomics Centre (NL)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-03-18
- DOI
- https://doi.org/10.1016/j.celrep.2025.115443
- Citations
- 5
- Primary Topic
- Cancer therapeutics and mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 4.03
Funders
- KWF Kankerbestrijding