High impact information on Cdc7

• Cdc7 kinase is essential for initiation of DNA replication [1].
• The impairment in spermatogenesis correlates with the extremely low level of Cdc7 protein in testes, and is rescued by introducing an additional allele of transgene, which results in increase of Cdc7 expression [1].
• Our results indicate the requirement of a critical level of a cell-cycle regulator for mouse development and provide genetic evidence that Cdc7 plays essential roles in meiotic processes in mammals [1].
• Inactivation of Cdc7 kinase in mouse ES cells results in S-phase arrest and p53-dependent cell death [2].
• Inhibition of p53 leads to partial rescue of muCdc7(-/-) ES cells from cell death. muCdc7(-/-)p53(-/-) embryos survive up to E8.5, and their blastocysts generate inner cell mass of a significant size in vitro, whereas those of the muCdc7(-/-)p53(+/-) embryos undergoes complete degeneration [2].

Biological context of Cdc7

• Cdc7-related kinases play essential roles in the initiation of yeast DNA replication [2].
• These results demonstrate that, in contrast to cell cycle arrest at the G(1)/S boundary observed in yeasts, loss of Cdc7 in ES cells results in rapid cessation of DNA synthesis within S phase, triggering checkpoint responses leading to recombinational repair and p53-dependent cell death [2].
• Phosphorylation of MCM4 by Cdc7 Kinase Facilitates Its Interaction with Cdc45 on the Chromatin [3].
• Cdc7(-/-) mouse embryonic stem (ES) cells are non-viable but their growth can be rescued by an ectopically expressed transgene (Cdc7(-/-)tg) [1].
• A regulatory subunit, Dbf4, stimulates the kinase activity of Cdc7 and recruits it to the replication origins [4].

Anatomical context of Cdc7

• 5. We have established a mutant embryonic stem (ES) cell line lacking the muCdc7 genes in the presence of a loxP-flanked transgene expressing muCdc7 cDNA [2].
• Cdc7-/- mice or embryonic fibroblast cells (MEFs) expressing a low level of transgene-encoded Cdc7 protein are viable but exhibit reduced body size with impaired germ cell development and decreased cell proliferation [5].

Associations of Cdc7 with chemical compounds

• Cdc7, a conserved serine/threonine protein kinase, controls initiation of DNA replication [4].
• Growth regulation of the expression of mouse cDNA and gene encoding a serine/threonine kinase related to Saccharomyces cerevisiae CDC7 essential for G1/S transition. Structure, chromosomal localization, and expression of mouse gene for s. cerevisiae Cdc7-related kinase [6].

Analytical, diagnostic and therapeutic context of Cdc7

• Genetic dissection of mammalian Cdc7 kinase: cell cycle and developmental roles [5].

References