Mechanistic basis for the spatiotemporal assembly of the Bloom Syndrome complex on ultrafine DNA bridges
- 1Genome Damage and Stability Centre, University of Sussex, Brighton, BN1 9RQ, United Kingdom
Abstract
The BTRR (BLM/TOP3A/RMI1/RMI2) complex resolves DNA replication and recombination intermediates, as well as mitotic DNA intertwinements, yet how its diverse activities are regulated remains unclear. Here, we identify key determinants of stable assembly of the BTRR complex on ultrafine DNA bridges (UFBs). We reveal that the RMI1-RMI2 subcomplex acts as a molecular reader of hydrophobic-rich short linear motifs (SLiMs) embedded within PICH and FANCM, thereby providing a conserved mechanism for engaging distinct Superfamily2 DNA translocases during chromosome segregation and DNA repair. During UFB resolution, SLiM binding stabilises the PICH-BTRR complex assembly and supports essential interactions among BLM, PICH, and DNA. Persistent PICH-BTRR complex association post-mitosis would compromise interphase DNA damage responses and is prevented by active PICH nuclear exclusion. Our findings define the molecular basis of UFB-binding complex assembly and highlight its spatiotemporal control required to specialise BTRR complex functions.
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BibTeX
@misc{aliyaskarova2026mechanistic,
title = {{Mechanistic basis for the spatiotemporal assembly of the Bloom Syndrome complex on ultrafine DNA bridges}},
author = {U. Aliyaskarova and O. Ozer and M. Sumon and E. Karanika and A. Crncec and Z. Kozik and T. Roumeliotis and J. Choudhary and M. Fernandez-Casanas and M. Day and A. W. Oliver and J. Pines and K.-L. Chan},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.750333},
url = {https://www.biorxiv.org/content/10.64898/2026.09.10.750333v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Mechanistic basis for the spatiotemporal assembly of the Bloom Syndrome complex on ultrafine DNA bridges
AU - U. Aliyaskarova
AU - O. Ozer
AU - M. Sumon
AU - E. Karanika
AU - A. Crncec
AU - Z. Kozik
AU - T. Roumeliotis
AU - J. Choudhary
AU - M. Fernandez-Casanas
AU - M. Day
AU - A. W. Oliver
AU - J. Pines
AU - K.-L. Chan
PY - 2026
DA - 2026/09/10
PB - bioRxiv
DO - 10.64898/2026.09.10.750333
UR - https://www.biorxiv.org/content/10.64898/2026.09.10.750333v1
AB - The BTRR (BLM/TOP3A/RMI1/RMI2) complex resolves DNA replication and recombination intermediates, as well as mitotic DNA intertwinements, yet how its diverse activities are regulated remains unclear. Here, we identify key determinants of stable assembly of the BTRR complex on ultrafine DNA bridges (UFBs). We reveal that the RMI1-RMI2 subcomplex acts as a molecular reader of hydrophobic-rich short linear motifs (SLiMs) embedded within PICH and FANCM, thereby providing a conserved mechanism for engaging distinct Superfamily2 DNA translocases during chromosome segregation and DNA repair. During UFB resolution, SLiM binding stabilises the PICH-BTRR complex assembly and supports essential interactions among BLM, PICH, and DNA. Persistent PICH-BTRR complex association post-mitosis would compromise interphase DNA damage responses and is prevented by active PICH nuclear exclusion. Our findings define the molecular basis of UFB-binding complex assembly and highlight its spatiotemporal control required to specialise BTRR complex functions.
ER -