Chapter 21 Regulation of the Eukaryotic Cell Cycle April 6, 2005 Presented by: Jennifer Payne

Sections within the Chapter §21.1 Overview of the Cell Cycle and Its Control §21.2 Biochemical Studies with Oocytes, Eggs, and Early Embryos §21.3 Genetic Studies with S. pombe §21.4 Molecular Mechanisms for Regulating Mitotic Events §21.5 Genetic Studies with S. cerevisiae §21.6 Cell-Cycle Control in Mammalian Cells §21.7 Checkpoints in Cell- Cycle Regulation

21.1 Overview of the Cell Cycle and Its Control §There are ordered series of events that eukaryotic cells proceed through, which constitutes the cell cycle. §During the cell cycle the cells chromosomes are duplicated and one copy of each of the chromosomes segregates into two daughter cells. §The regulation of the cell cycle is essential for normal cell development of multicellular organisms. Any loss of control can result in cancer, a disease that leads to death in one in every six people.

Overview continued §Cell replication is primarily controlled by regulating the timing of two critical events in the cell cycle: nuclear DNA replication and mitosis. §The main controllers of these events are heterodimeric protein kinases that contain a regulatory subunit and a catalytic subunit. §The kinases regulate the activities of multiple proteins involved in DNA replication and mitosis by phosphorylating them at specific regulatory sites, activating some and inhibiting others to coordinate their activities.

The Ordered Series of Events Leading to Replication of Cells §The cell cycle is divided into four major phases: 1. S phase 2. G 2 phase 3. M phase 4. G 1 phase §Each of these phases have their own series of events until the cell is duplicated into two daughter cells at the end of the M phase. §The M phase is when the process of mitosis occurs.

Four Phases of the Cell Cycle §In the S (synthesis phase) the chromosomes are replicated. §After the cell progresses through the G 2 phase the cell then begins mitosis. §Mitosis occurs during the M phase of the cell cycle. Mitosis is divided into several different stages.

Mitosis

Following Mitosis §The G 1 phase follows mitosis. This phase is the period before DNA synthesis is reinitiated into the S phase. §In vertebrates and diploid yeasts the cells in G 1 have a diploid number of chromosomes (2n), one inherited from each parent. §In haploid yeasts, cells in G 1 have one of each chromosome (1n).

Length of the Cell Cycle §There are rapidly replicating human cells that progress through the entire cell cycle in approximately 24 hours. §Mitosis takes around 30 minutes; G 1, 9 hours; S phase, 10 hours; and G 2, 4.5 hours. §In growing yeast cells the cycle only takes about 90 minutes combined.

Postmitotic Cells §The postmitotic cells can leave the cell cycle and remain for days, weeks, or sometimes the lifetime of the organism. §Cells that remain the lifetime of the organism does not proliferate any further. §In vertebrates cells leave the cell cycle in G 1 phase and enter into a phase called G 0. §G 0 cells returning to the cell cycle enter into the S phase.

A Pictorial Representation of the Cell Cycle