Topic
Geminin
About: Geminin is a research topic. Over the lifetime, 332 publications have been published within this topic receiving 16649 citations. The topic is also known as: Gem & MGORS6.
Papers published on a yearly basis
Papers
TL;DR: It is suggested that geminin inhibits inappropriate origin firing by targeting Cdt1, a recently identified replication initiation factor necessary for MCM loading in Multicellular eukaryotes.
Abstract: In all eukaryotic organisms, inappropriate firing of replication origins during the G2 phase of the cell cycle is suppressed by cyclin-dependent kinases. Multicellular eukaryotes contain a second putative inhibitor of re-replication called geminin. Geminin is believed to block binding of the mini-chromosome maintenance (MCM) complex to origins of replication, but the mechanism of this inhibition is unclear. Here we show that geminin interacts tightly with Cdt1, a recently identified replication initiation factor necessary for MCM loading. The inhibition of DNA replication by geminin that is observed in cell-free DNA replication extracts is reversed by the addition of excess Cdt1. In the normal cell cycle, Cdt1 is present only in G1 and S, whereas geminin is present in S and G2 phases of the cell cycle. Together, these results suggest that geminin inhibits inappropriate origin firing by targeting Cdt1.
744 citations
TL;DR: This work has shown that Geminin plays a crucial role in inhibiting licensing in metazoans and, like cyclins, is inactivated by the APC/C, which ensures that no origin can fire more than once in a cell cycle.
433 citations
TL;DR: H4 acetylation at origins by HBO1 is critical for replication licensing by Cdt1, and negative regulation of licensing by Geminin is likely to involve inhibition of HBO1 histone acetylase activity.
257 citations
TL;DR: It is indicated that both cyclin A and geminin are required for the suppression of overreplication and for genome stability in Drosophila cells.
Abstract: Alteration of the control of DNA replication and mitosis is considered to be a major cause of genome instability. To investigate the mechanism that controls DNA replication and genome stability, we used the RNA silencing-interference technique (RNAi) to eliminate the Drosophila geminin homologue from Schneider D2 (SD2) cells. Silencing of geminin by RNAi in SD2 cells leads to the cessation of mitosis and asynchronous overreplication of the genome, with cells containing single giant nuclei and partial ploidy between 4N and 8N DNA content. The effect of geminin deficiency is completely suppressed by cosilencing of Double parked (Dup), the Drosophila homologue of Cdt1, a replication factor to which geminin binds. The geminin deficiency-induced phenotype is also partially suppressed by coablation of Chk1/Grapes, indicating the involvement of Chk1/Grapes in the checkpoint control in response to overreplication. We found that the silencing of cyclin A, but not of cyclin B, also promotes the formation of a giant nucleus and overreplication. However, in contrast to the effect of geminin knockout, cyclin A deficiency leads to the complete duplication of the genome from 4N to 8N. We observed that the silencing of geminin causes rapid downregulation of Cdt1/Dup, which may contribute to the observed partial overreplication in geminin-deficient cells. Analysis of cyclin A and geminin double knockout suggests that the effect of cyclin A deficiency is dominant over that of geminin deficiency for cell cycle arrest and overreplication. Together, our studies indicate that both cyclin A and geminin are required for the suppression of overreplication and for genome stability in Drosophila cells.
209 citations
TL;DR: It is demonstrated that human Cdt1 is phosphorylated by cyclin A-dependent kinases dependent on its cyclin-binding motif, and inactivation of Cdk1 results in Cdt 1 dephosphorylation and rebinding to chromatin in murine FT210 cells synchronized around the G2/M phase, suggesting thatCdt1 function is also negatively regulated by the Cdk phosphorylation independent of geminin binding.
204 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2022 | 1 |
| 2021 | 3 |
| 2020 | 8 |
| 2019 | 10 |
| 2018 | 10 |
| 2017 | 17 |