Franz, Andre, Orth, Michael, Pirson, Paul A., Sonneville, Remi, Blow, J. Julian ORCID: 0000-0002-9524-5849, Gartner, Anton ORCID: 0000-0003-4639-9902, Stemmann, Olaf ORCID: 0000-0003-3044-2515 and Hoppe, Thorsten ORCID: 0000-0002-4734-9352 (2011). CDC-48/p97 Coordinates CDT-1 Degradation with GINS Chromatin Dissociation to Ensure Faithful DNA Replication. Mol. Cell, 44 (1). S. 85 - 97. CAMBRIDGE: CELL PRESS. ISSN 1097-4164

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Franz, AndreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Orth, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pirson, Paul A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sonneville, RemiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blow, J. JulianUNSPECIFIEDorcid.org/0000-0002-9524-5849UNSPECIFIED
Gartner, AntonUNSPECIFIEDorcid.org/0000-0003-4639-9902UNSPECIFIED
Stemmann, OlafUNSPECIFIEDorcid.org/0000-0003-3044-2515UNSPECIFIED
Hoppe, ThorstenUNSPECIFIEDorcid.org/0000-0002-4734-9352UNSPECIFIED
URN: urn:nbn:de:hbz:38-487437
DOI: 10.1016/j.molcel.2011.08.028
Journal or Publication Title: Mol. Cell
Volume: 44
Number: 1
Page Range: S. 85 - 97
Date: 2011
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4164
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
XENOPUS EGG EXTRACTS; UBIQUITIN-SELECTIVE CHAPERONE; AAA ATPASE CDC48/P97; CAENORHABDITIS-ELEGANS; CELL-CYCLE; C-ELEGANS; S-PHASE; PROTEIN-DEGRADATION; GENOME STABILITY; CDC45Multiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48743

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