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
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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CDC2-CDC28 Kinases*
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Carrier Proteins*
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Cell Cycle Proteins*
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Cell Division
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Cyclin E / metabolism
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinases / metabolism
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Cyclins / metabolism
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DNA Damage / genetics*
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DNA-Binding Proteins*
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E2F Transcription Factors
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G1 Phase*
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Neoplasms / genetics
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Neoplasms / pathology
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins c-myc / metabolism
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Retinoblastoma Protein / metabolism
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Retinoblastoma-Binding Protein 1
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S Phase*
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Signal Transduction
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Transcription Factors / metabolism
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Tumor Suppressor Protein p53 / metabolism
Substances
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Carrier Proteins
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Cell Cycle Proteins
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Cyclin E
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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DNA-Binding Proteins
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E2F Transcription Factors
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Proto-Oncogene Proteins c-myc
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Retinoblastoma Protein
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Retinoblastoma-Binding Protein 1
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Transcription Factors
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Tumor Suppressor Protein p53
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Protein Serine-Threonine Kinases
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CDC2-CDC28 Kinases
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases