Pathways governing G1/S transition and their response to DNA damage

FEBS Lett. 2001 Feb 16;490(3):117-22. doi: 10.1016/s0014-5793(01)02114-7.

Abstract

The ability to self-replicate is a fundamental feature of life, reflected at the cellular level by a highly regulated process initiated in G1 phase via commitment to a round of DNA replication and cell division. Here we briefly highlight recent advances in understanding the molecular pathways which govern the decision of mammalian somatic cells to enter S phase, and the so-called cell cycle checkpoints which guard the G1/S transition and S phase progression against potentially deleterious effects of genotoxic stress. Particular emphasis is put on the emerging parallel yet cooperative pathways of retinoblastoma protein (pRB)-E2F and Myc, their convergence to control the activity of the cyclin-dependent kinase 2 (Cdk2) at the G1/S boundary, as well as the two waves of checkpoint responses at G1/S: the rapid pathway(s) leading to Cdc25A degradation, and the delayed p53-p21 cascade, both silencing the Cdk2 activity upon DNA damage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CDC2-CDC28 Kinases*
  • Carrier Proteins*
  • Cell Cycle Proteins*
  • Cell Division
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / metabolism
  • DNA Damage / genetics*
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • G1 Phase*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • Retinoblastoma Protein / metabolism
  • Retinoblastoma-Binding Protein 1
  • S Phase*
  • Signal Transduction
  • Transcription Factors / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • Cyclin E
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • Proto-Oncogene Proteins c-myc
  • Retinoblastoma Protein
  • Retinoblastoma-Binding Protein 1
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases