SP9: Mutual impact of replication origin firing regulation and mitotic chromosome segregation

We intend to shed light on the interplay between the regulation of replication origin firing and mitotic chromosome segregation. The relationship between faithful genome replication and chromosome segregation is mutual: de-regulated genome replication causes replication stress and chromosome missegregation [1, 2]. Conversely, chromosome missegregation causes replication stress [3, 4]. Although it is clear that proper regulation of origin firing, the main focus of our lab, is key for complete and faithful genome replication, it remains largely unexplored how the faithful regulation of origin firing and faithful chromosome segregation are interlinked. This is partly because the complexity of origin firing regulation is only beginning to be revealed [5]. We have described a main regulation platform of replication origin firing, the MTBP-Treslin-TopBP1 protein complex and shown that it mediates classic cell cycle and DNA damage-dependent regulations [6, 7]. Recently, we found that, in addition to these roles that are conserved throughout eukaryotes, MTBP and Treslin also mediate vertebrate-specific fine-regulation of origin firing that is required to prevent replication stress [8][9] (Ferreira et al. bioRxiv 2021). Building on this latest insight on origin firing regulation, we aim to better understand the connection between origin firing de-regulation and mitotic dysfunction.