Abstract
Most eukaryotic cells become committed to divide once DNA synthesis begins. This critical event is controlled in yeast and Xenopus oocytes by the degradation of cyclin inhibitory proteins, while in mammalian cells over-expression of cyclin E or cyclin D1 promotes rapid entry into DNA synthesis. Curiously, however, this over-expression also lengthens S phase and promotes DNA damage. To directly assess the roles of the cyclin inhibitory protein p27Kip1 (p27) and of cyclin D1 in the regulation of DNA synthesis initiation in mammalian cells, we have utilized a quantitative cytometric approach for the study of cell cycle control in actively proliferating cultures. As evidence that p27 plays a direct role in regulating entry into S phase, we find that its levels fall at the time of DNA synthesis initiation in NIH3T3 cells, and that its suppression shortens G1 phase and shortens the length of the entire cell cycle. In this function, however, the action of p27 appears to be linked with cyclin D1. G1-S phase transition is efficiently blocked by p27 unless excess cyclin D1 is present. These two proteins are coordinately regulated by the cell, and are maintained at a nearly constant ratio throughout an actively proliferating culture. We propose that p27 directly regulates the initiation of DNA synthesis in NIH3T3 cells, and that cyclin D1 serves to modulate this activity.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.