title: CDC-48/p97 coordinates CDT-1 degradation with GINS chromatin dissociation to ensure faithful DNA replication.
abstract: Faithful transmission of genomic information requires tight spatiotemporal regulation of DNA replication factors. In the licensing step of DNA replication, CDT-1 is loaded onto chromatin to subsequently promote the recruitment of additional replication factors, including CDC-45 and GINS. During the elongation step, the CDC-45/GINS complex moves with the replication fork; however, it is largely unknown how its chromatin association is regulated. Here, we show that the chaperone-like ATPase CDC-48/p97 coordinates degradation of CDT-1 with release of the CDC-45/GINS complex. C. elegans embryos lacking CDC-48 or its cofactors UFD-1/NPL-4 accumulate CDT-1 on mitotic chromatin, indicating a critical role of CDC-48 in CDT-1 turnover. Strikingly, CDC-48(UFD-1/NPL-4)-deficient embryos show persistent chromatin association of CDC-45/GINS, which is a consequence of CDT-1 stabilization. Moreover, our data confirmed a similar regulation in Xenopus egg extracts, emphasizing a conserved coordination of licensing and elongation events during eukaryotic DNA replication by CDC-48/p97.
authors: Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Zülpicher Strasse 47a, 50674 Cologne, Germany.
authors: André
authors: A
authors: Franz
authors: Michael
authors: M
authors: Orth
authors: Paul A
authors: PA
authors: Pirson
authors: Remi
authors: R
authors: Sonneville
authors: J Julian
authors: JJ
authors: Blow
authors: Anton
authors: A
authors: Gartner
authors: Olaf
authors: O
authors: Stemmann
authors: Thorsten
authors: T
authors: Hoppe
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004261:DNA Replication; D008025:Ligases / Q000378:metabolism*; D008297:Male; D008938:Mitosis; D034622:RNA Interference; D013094:Spermatozoa / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism; D000074405:Valosin Containing Protein; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D029742:Caenorhabditis elegans Proteins; C502211:Cdc45 protein, Xenopus; C475683:Cdt-1 protein, C elegans; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D025801:Ubiquitin; D029867:Xenopus Proteins; C000608563:evl-18 protein, C elegans; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein; D008025:Ligases