| First Author | Coulombe P | Year | 2013 |
| Journal | Nat Commun | Volume | 4 |
| Pages | 2065 | PubMed ID | 23817338 |
| Mgi Jnum | J:223504 | Mgi Id | MGI:5649224 |
| Doi | 10.1038/ncomms3065 | Citation | Coulombe P, et al. (2013) A spontaneous Cdt1 mutation in 129 mouse strains reveals a regulatory domain restraining replication licensing. Nat Commun 4:2065 |
| abstractText | Cdt1 is required for loading the replicative DNA helicase MCM2/7, a process known as DNA replication licensing. Here we show that 129 mouse strains express a Cdt1 mutated allele with enhanced licensing activity. The mutation, named Delta(6)PEST, involves a six-amino acid deletion within a previously uncharacterized PEST-like domain. Cdt1 Delta(6)PEST and more extensive deletions exhibit increased re-replication and transformation activities that are independent of the Geminin and E3 ligase pathways. This PEST domain negatively regulates cell cycle-dependent chromatin recruitment of Cdt1 in G2/M phases of the cell cycle. Mass spectrometry analysis indicates that Cdt1 is phosphorylated at sites within the deleted PEST domain during mitosis. This study reveals a conserved new regulatory Cdt1 domain crucial for proper DNA licensing activity and suggests a mechanism by which the presence of Cdt1 in G2/M phases does not lead to premature origin licensing. These results also question the usage of 129 mouse strains for knockout analyses. |
