XXXX ubiquitin ligase maintains genome stability by restraining DNA-replication licensing.

@entity72263 @entity2199 @entity72264
To maintain genome stability, DNA replication is strictly regulated to occur only once per cell cycle. In eukaryotes, the presence of 'licensing proteins' at replication origins during the G1 cell-cycle phase allows the formation of the pre-replicative complex. The removal of licensing proteins from chromatin during the S phase ensures that origins fire only once per cell cycle. Here we show that the @entity72263 ubiquitin ligase temporally restricts DNA-replication licensing in @entity2199 . Inactivation of @entity72263 causes massive DNA re-replication, producing cells with up to 100C DNA content. The @entity2199 orthologue of the replication-licensing factor @entity72264 (refs 2, 3) is required for DNA replication. @entity2199 @entity72264 is present in G1-phase nuclei but disappears as cells enter S phase. In cells lacking @entity72263 , @entity72264 levels fail to decrease during S phase and instead remain constant in the re-replicating cells. Removal of one genomic copy of @entity72264 suppresses the @entity72263 re-replication phenotype. We propose that @entity72263 prevents aberrant re-initiation of DNA replication, at least in part, by facilitating the degradation of @entity72264 .
