@article{ee6bb3e0533911dd8d9f000ea68e967b,
title = "Human geminin promotes pre-RC formation and DNA replication by stabilizing CDT1 in mitosis.",
abstract = "Geminin is an unstable inhibitor of DNA replication that negatively regulates the licensing factor CDT1 and inhibits pre-replicative complex (pre-RC) formation in Xenopus egg extracts. Here we describe a novel function of Geminin. We demonstrate that human Geminin protects CDT1 from proteasome-mediated degradation by inhibiting its ubiquitination. In particular, Geminin ensures basal levels of CDT1 during S phase and its accumulation during mitosis. Consistently, inhibition of Geminin synthesis during M phase leads to impairment of pre-RC formation and DNA replication during the following cell cycle. Moreover, we show that inhibition of CDK1 during mitosis, and not Geminin depletion, is sufficient for premature formation of pre-RCs, indicating that CDK activity is the major mitotic inhibitor of licensing in human cells. Taken together with recent data from our laboratory, our results demonstrate that Geminin is both a negative and positive regulator of pre-RC formation in human cells, playing a positive role in allowing CDT1 accumulation in G2-M, and preventing relicensing of origins in S-G2.",
author = "Andrea Ballabeni and Marina Melixetian and Raffaella Zamponi and Laura Masiero and Federica Marinoni and Kristian Helin",
note = "Keywords: Animals; Cell Cycle Proteins; Cell Line, Tumor; Cercopithecus aethiops; Cyclin-Dependent Kinases; DNA; DNA Replication; Enzyme Activation; G1 Phase; Gene Deletion; Gene Expression Regulation; Humans; Mitosis; Proteasome Endopeptidase Complex; Protein Binding; Ubiquitins",
year = "2004",
doi = "10.1038/sj.emboj.7600314",
language = "English",
volume = "23",
pages = "3122--32",
journal = "E M B O Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "15",
}