p53 and pRb prevent rereplication in response to microtubule inhibitors by mediating a reversible G1 arrest

Cancer Res. 1998 Feb 1;58(3):396-401.


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.

MeSH terms

  • Aneuploidy
  • Antineoplastic Agents / pharmacology
  • Cell Cycle
  • Cells, Cultured
  • Cyclin-Dependent Kinase Inhibitor p16 / physiology
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / physiology
  • DNA Replication / drug effects*
  • Fibroblasts / drug effects
  • G1 Phase / drug effects*
  • Humans
  • Microtubules / drug effects*
  • Nocodazole / pharmacology*
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Retinoblastoma Protein / deficiency
  • Retinoblastoma Protein / pharmacology
  • Retinoblastoma Protein / physiology*
  • Tumor Suppressor Protein p53 / deficiency
  • Tumor Suppressor Protein p53 / pharmacology
  • Tumor Suppressor Protein p53 / physiology*


  • Antineoplastic Agents
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • Nocodazole