Handout for Cell Cycle Regulation

(November 1 and 3, 2004, in Shanghai; November 5, 2004, in Beijing)

Hui Zhang, Ph. D.

I-138, Sterling Hall of Medicine
Department of Genetics
Yale University School of Medicine
333 Cedar Street
New Haven, CT 06520, USA
Telephone: (203)737-1922; Fax: (203)785-7023; E-mail: hui.zhang@yale.edu

I. “Cell” as a basic unit of living organisms:

a. Single cell and multicellular organisms
b. Multicellular organims are developed from a single cell---cell
proliferation, differentiation, and regulated cell death
c. Cell proliferation by cell duplication and cell division
d. Symmetric and asymmetric cell divisions

II. Stone-ages of cell cycle/ cell division analysis

a. Nuclear division and cytokinesis
b. Chromosomes and mitosis
c. Centromeres and centrosomes
d. Mitosis versus meiosis

III. Cell cycle is a cycle is a cycle is a cycle…

a. Cell cycle can be divided into G1, S, G2, and M phases
b. G0 phase and cellular aging/senescence
c. Cell cycle is a one way traffic

IV. Cell cycle is regulated by specific factors in each cell cycle phase
a. Cell fusion experiment
b. Maturation promoting factor (MPF)
c. The cdc mutants

V. The master regulator of cell cycle-CDC2

a. Isolation of cdc2 mutants in fission yeast Schizosaccharomyces pombe
and its homologue cdc28 in budding yeast Saccharomyces cerevisiae
b. CDC2 is highly conserved and is a component of MPF
c. Multiple CDKs in high eukaryotes

VI. Surfing cyclin waves-Oscillation is the key

a. Oscillation of cyclins---discovery
b. cyclins are regulatory subunits of CDC2
 c. different cyclins regulate cell cycle progression
d. cyclins are regulated by synthesis and protein degradation

VII. To condense and segregate-Regulation of CDC2 activity in mitosis

a. CDC25/Wee1
b. Anaphase-promoting complex/cyclosome
c. Chromosome condensation, segregation, and exit of mitosis
d. Spindle checkpoint and G2/M cell cycle arrest by DNA damage agents

VIII. To grow or not to grow-Regulation of G1 phase

a. G1 specific cyclins and CDK complexes
b. CDK inhibitors
c. Restriction point and checkpoint
d. Retinoblastoma susceptibility gene product (Rb) and p53
e. SCF ubiquitin E3 ligase complexes

IX. To duplicate and double your genetic material-S phase regulation

a. S-phase specific cyclins
b. replication origins
c. cell cycle control of replication origins
d. coupling replication to mitosis

X. When to cycle-Cell cycle and cancer

a. Alteration of cell cycle regulation is a hallmark of human cancer
b. Dysregulation of cyclins and CDK inhibitors
c. Control of genome stability

XI. To make different cells-Cell cycle and development

a. Molecular aspects of meiosis
b. Molecular mechanism of asymmetric cell division
c. Cell fate determination---germ cells and somatic cells

Reviews:

Sherr, C. J. 2004. Principles of tumor suppression. Cell 116, 235-246. (PDF)

Seshan A, Amon A. 2004. Linked for life: temporal and spatial coordination
of late mitotic events. Curr Opin Cell Biol. Feb;16(1):41-8. (PDF)

Bardin, A. J. and Amon, A. 2001. Men and SIN: What’s the difference?
Nature Reviews 2: 815-826. (PDF)

Malumbers, M. and Barbacid, M. 2001. To cycle or not to cycle: a critical

decision in cancer. Nature Reviews 1: 222-231. (PDF)
Research papers for journal club:

Wei W, Ayad NG, Wan Y, Zhang GJ, Kirschner MW, Kaelin WG Jr. 2004.
Degradation of the SCF component Skp2 in cell-cycle phase G1 by the
anaphase-promoting complex. Nature 428:194-8. (PDF)

Bashir T, Dorrello NV, Amador V, Guardavaccaro D, Pagano M. 2004.

Control of the SCF(Skp2-Cks1) ubiquitin ligase by the APC/C(Cdh1)
ubiquitin ligase. Nature 428:190-3.