Is there a pre-RC checkpoint that cancer cells lack?
Critical for genomic integrity, accurate DNA replication is tightly regulated by the convergence of prereplication protein complexes (pre-RCs) to "license" replicating origins on DNA in G(1) and is activated by S-phase promoting kinases that selectively target and trigger origin firing in S-phase. To present, a checkpoint mechanism monitoring pre-RC complex formation and activation has yet to be elucidated. However, perturbation of these protein complexes has yielded divergent phenotypes in recent reports: normal cells arrest in the cell cycle, whereas cancerous cells arrest and die. These data implicate a mechanism by which normal cells sense pre-RC deficiency and then signal for cell cycle arrest. The potential for therapeutic exploits of this disparity between normal and cancer cells is apparent. Here, we explore recent data supporting the existence of a pre-RC checkpoint that ensures faithful pre-RC formation, a cell cycle mechanism that is intriguingly compromised in cancer cells.
Lau
Eric
E
The Burnham Institute for Medical Research, La Jolla, California 92037, USA.
Jiang
Wei
W
D000818:Animals; D004261:DNA Replication / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy