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fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Green, C. M. (2006)
Publisher: Elsevier
Languages: English
Types: Article
Subjects: QD, QH301, R1
To prevent duplication or loss of genomic regions during DNA replication, it is essential that the entire genome is copied precisely once every S phase. Cells achieve this by mutually exclusive regulation of origin firing and licensing. A crucial protein that is involved in origin licensing is chromatin licensing and DNA replication factor 1 (CDT1) and, therefore, activity of this protein must be strictly controlled. Four recent articles have demonstrated that proliferating cell nuclear antigen (PCNA), an essential sliding clamp used in replication and DNA repair, has a crucial role in this process by mediating the proteasomal degradation of CDT1.
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    • 1. Blow, J.J. and A. Dutta, Preventing re-replication of chromosomal DNA. Nat Rev Mol Cell Biol, 2005. 6(6): p. 476-486.
    • 2. Diffley, J.F., Regulation of early events in chromosome replication. Curr Biol, 2004. 14(18): p. R778-786.
    • 3. Saxena, S. and A. Dutta, Geminin-Cdt1 balance is critical for genetic stability. Mutat Res, 2005. 569(1-2): p. 111-121.
    • 4. Hu, J., et al., Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage. Nat Cell Biol, 2004. 6(10): p. 1003-1009.
    • 5. Kondo, T., et al., Rapid degradation of Cdt1 upon UV-induced DNA damage is mediated by SCFSkp2 complex. J Biol Chem, 2004. 279(26): p. 27315- 27319.
    • 6. Li, X., et al., The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation. J Biol Chem, 2003. 278(33): p. 30854-30858.
    • 7. Zhong, W., et al., CUL-4 ubiquitin ligase maintains genome stability by restraining DNA-replication licensing. Nature, 2003. 423(6942): p. 885-889.
    • 8. Arias, E.E. and J.C. Walter, PCNA functions as a molecular platform to trigger Cdt1 destruction and prevent re-replication. Nat Cell Biol, 2006. 8(1): p. 84-90.
    • 9. Hu, J. and Y. Xiong, An evolutionarily conserved function of proliferating cell nuclear antigen for Cdt1 degradation by the Cul4-Ddb1 ubiquitin ligase in response to DNA damage. J Biol Chem, 2006. 281(7): p. 3753-3756.
    • 10. Nishitani, H., et al., Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis. Embo J, 2006. 25(5): p. 1126-1136.
    • 11. Senga, T., et al., PCNA is a cofactor for Cdt1 degradation by CUL4/DDB1- mediated N-terminal ubiquitination. J Biol Chem, 2006. 281(10): p. 6246- 6252.
    • 12. Maga, G. and U. Hubscher, Proliferating cell nuclear antigen (PCNA): a dancer with many partners. J Cell Sci, 2003. 116(Pt 15): p. 3051-3060.
    • 13. Warbrick, E., The puzzle of PCNA's many partners. Bioessays, 2000. 22(11): p. 997-1006.
    • 14. Arias, E.E. and J.C. Walter, Replication-dependent destruction of Cdt1 limits DNA replication to a single round per cell cycle in Xenopus egg extracts. Genes Dev, 2005. 19(1): p. 114-126.
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