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First published online 16 June 2009
doi: 10.1242/jcs.042861
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Research Article |
1 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
2 Institute of Molecular Biology, Academia Sinica, 128, Sec No. 2, Academia Road, Taipei 115, Taiwan
3 Department of Medical Research, National Taiwan University Hospital, No. 7, Chung San South Road, Taipei 115, Taiwan
4 Gratuate Institute of Molecular Medicine, Medical College, National Taiwan University. No. 1, Ren-Ai Road Section 1., Taipei 100, Taiwan
5 Department of Life Science, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-San, Tao-Yuan 333, Taiwan
* Author for correspondence (e-mail: ctchien{at}gate.sinica.edu.tw)
Accepted 1 April 2009
In higher eukaryotes, the pre-replication complex (pre-RC) component Cdt1 is the major regulator in licensing control for DNA replication. The Cul4-DDB1-based ubiquitin ligase mediates Cdt1 ubiquitylation for subsequent proteolysis. During the initiation of chorion gene amplification, Double-parked (Dup), the Drosophila ortholog of Cdt1, is restricted to chorion gene foci. We found that Dup accumulated in nuclei in Cul4 mutant follicle cells, and the accumulation was less prominent in DDB1 mutant cells. Loss of Cul4 or DDB1 activity in follicle cells also compromised chorion gene amplification and induced ectopic genomic DNA replication. The focal localization of Orc2, a subunit of the origin recognition complex, is frequently absent in Cul4 mutant follicle cells. Therefore, Cul4 and DDB1 have differential functions during chorion gene amplification.
Key words: Cul4, DDB1, Proliferation, DNA replication, pre-RC, Dup, Cdt1, Orc2, Chorion gene amplification
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