SRBD1, a highly conserved gene required for chromosome individualization
Year: 2025
Type: article
Abstract: 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.
Source: Cell Reports
Authors: Jonne A. Raaijmakers, Louise M.E. Janssen, Abdelghani Mazouzi, Amber L.H. Hondema, Razvan Borza, Alexander Fish, Ahmed M.O. Elbatsh, Justina Kazokaitė-Adomaitienė, Nuria Vaquero-Siguero, Isabel Mayayo-Peralta, Leila Nahidiazar, Anoek Friskes, Liesbeth Hoekman, Onno B. Bleijerveld, Claire Hoencamp, Sarah C. Moser, Jos Jonkers, Kees Jalink, Wilbert Zwart, Patrick H.N. Celie, Benjamin D. Rowland, Anastassis Perrakis, Thijn R. Brummelkamp, René H. Medema
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funder: KWF Kankerbestrijding
OpenAlex ID: W4408561207