Molecular Genetics

A cell's commitment to DNA replication occurs considerably before DNA synthesis begins.

Facts

	Placing a nucleus from a G1 cell into a cell whose nucleus is in S phase (left) results in initiation of DNA synthesis in the G1 nucleus. Mammalian cells in culture require serum. The effects on DNA synthesis of serum deprivation at various times during G1 and S were determined (below; solid bars = presence of serum; open bars = absence of serum).
Transcription of numerous genes producing proteins required in DNA synthesis occurs during a limited period late in G1. Genes for the p34-like cyclin-dependent kinase are essential for entry into S phase. Novel cyclins appear late in G1.

Interpretations

• Cytoplasmic factors produced in late G1 are required for initiation of S.
• A point of commitment to initiation of S occurs in G1. After this point (called restriction point or START, depending on the organism) the machinery has been set in motion to initiate DNA synthesis.
• The machinery includes the transcription of genes responsible for DNA synthesis proteins.
• A cyclin-dependent phosphorylation cascade is involved in the regulation pathway around START.
• Serum deprivation can be used to synchronize a population of cells.

Further information

• Various proteins act as check points at different points in the cycles.
• The signal(s) that trigger START are still under investigation.

This is page 1332 of Molecular Genetics by Ulrich Melcher, © 1997, 1998, 1999