PT  - JOURNAL ARTICLE
AU  - Khan, Shireen Hussain
AU  - Wahl, Geoffrey M.
TI  - p53 and pRb Prevent Rereplication in Response to Microtubule Inhibitors by Mediating a Reversible G<sub>1</sub> Arrest
DP  - 1998 Feb 01
TA  - Cancer Research
PG  - 396--401
VI  - 58
IP  - 3
4099  - http://cancerres.aacrjournals.org/content/58/3/396.short
4100  - http://cancerres.aacrjournals.org/content/58/3/396.full
SO  - Cancer Res1998 Feb 01; 58
AB  - Cell cycle checkpoints are safeguards that ensure the initiation of downstream events only after completion of upstream processes. The tumor suppressors p53 and pRb prevent initiation of a second round of replication in response to spindle inhibitors, but it has yet to be proven that this is a mitotic checkpoint response. We show that asynchronous human fibroblasts arrest in G1 with 4 N DNA content after nocodazole treatment, whereas isogenic p53- and pRb-deficient fibroblasts rereplicate. Importantly, nocodazole elicits a reversible arrest in G0-G1 synchronized normal human fibroblasts but not in isogenic p53-deficient derivatives. Furthermore, the G1 cyclin-dependent kinase inhibitors p21 and p16 also play critical roles in limiting rereplication. Hence, p53 and pRb are required during G1 to prevent entry into a replicative cycle and appear to provide a connection between the structural integrity of the microtubules and the cell cycle machinery in interphase cells. ©1998 American Association for Cancer Research.