RT Journal Article
SR Electronic
T1 FBL17 targets CDT1a for degradation in early S-phase to prevent Arabidopsis genome instability
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 774109
DO 10.1101/774109
A1 Bénédicte Desvoyes
A1 Sandra Noir
A1 Kinda Masoud
A1 María Isabel López
A1 Pascal Genschik
A1 Crisanto Gutierrez
YR 2019
UL http://biorxiv.org/content/early/2019/09/20/774109.abstract
AB Maintenance of genome integrity depends on controlling the availability of DNA replication initiation proteins, e.g., CDT1, a component of the pre-replication complexes that regulates chromatin licensing for replication. To understand the evolutionary history of CDT1 regulation, we have identified the mechanisms involved in CDT1 dynamics. During cell cycle, CDT1a starts to be loaded early after mitotic exit and maintains high levels until the G1/S transition. Soon after the S-phase onset, CDT1a is rapidly degraded in a proteasome-dependent manner. Plant cells use a specific SCF-mediated pathway that relies on the FBL17 F-box protein for CDT1a degradation, which is independent of CUL4a-containing complexes. A similar oscillatory pattern occurs in endoreplicating cells, where CDT1a is loaded just after finishing the S-phase. CDT1a is necessary to maintain genome stability, an ancient strategy although unique proteins and mechanisms have evolved in different eukaryotic lineages to ensure its degradation during S-phase.Impact statement The DNA replication protein CDT1a is crucial for genome integrity and is targeted for proteasome degradation just after S-phase initiation by FBL17 in proliferating and endoreplicating cells of Arabidopsis