Abstract

Cell cycle progression in mammals is modulated by two ubiquitin ligase complexes, CRL4 and SCF, which facilitate degradation of chromatin substrates involved in the regulation of DNA replication. One member of the CRL4 complex, the WD-40 containing protein RepID (DCAF14/PHIP), selectively binds and activates a group of replication origins. Here we show that RepID recruits the CRL4 complex to chromatin prior to DNA synthesis, thus playing a crucial architectural role in the proper licensing of chromosomes for replication. In the absence of RepID, cells rely on the alternative ubiquitin ligase, SKP2-containing SCF, to progress through the cell cycle. RepID depletion markedly increases cellular sensitivity to SKP2 inhibitors, which triggered massive genome re-replication. Both RepID and SKP2 interact with distinct, non-overlapping groups of replication origins, suggesting that selective interactions of replication origins with specific CRL components execute the DNA replication program and maintain genomic stability by preventing re-initiation of DNA replication.

Details

Title
The replication initiation determinant protein (RepID) modulates replication by recruiting CUL4 to chromatin
Author
Sang-Min, Jang 1 ; Zhang, Ya 1 ; Utani, Koichi 1 ; Fu, Haiqing 1 ; Redon, Christophe E 1 ; Marks, Anna B 1 ; Smith, Owen K 1 ; Redmond, Catherine J 1 ; Baris, Adrian M 1 ; Tulchinsky, Danielle A 1 ; Aladjem, Mirit I 1 

 Developmental Therapeutics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA 
Pages
1-13
Publication year
2018
Publication date
Jul 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2071157994
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.