Talk:2009 Lecture 15

From CellBiology


CDC6: from DNA replication to cell cycle checkpoints and oncogenesis. Borlado LR, Méndez J. Carcinogenesis. 2008 Feb;29(2):237-43. Epub 2007 Nov 28. Review. PMID: 18048387

Cell division cycle 6 (CDC6) is an essential regulator of DNA replication in eukaryotic cells. Its best-characterized function is the assembly of prereplicative complexes at origins of replication during the G(1) phase of the cell division cycle. However, CDC6 also plays important roles in the activation and maintenance of the checkpoint mechanisms that coordinate S phase and mitosis, and recent studies have unveiled its proto-oncogenic activity. CDC6 overexpression interferes with the expression of INK4/ARF tumor suppressor genes through a mechanism involving the epigenetic modification of chromatin at the INK4/ARF locus. In addition, CDC6 overexpression in primary cells may promote DNA hyperreplication and induce a senescence response similar to that caused by oncogene activation. These findings indicate that deregulation of CDC6 expression in human cells poses a serious risk of carcinogenesis.

Cardiac progenitors and the embryonic cell cycle. Goetz SC, Conlon FL. Cell Cycle. 2007 Aug 15;6(16):1974-81. Epub 2007 Jun 13. Review. PMID: 17712230

From cell cycle to differentiation: an expanding role for cdk6. Grossel MJ, Hinds PW. Cell Cycle. 2006 Feb;5(3):266-70. Epub 2006 Feb 6. Review. PMID: 1641072

Cell cycle sibling rivalry: Cdc2 vs. Cdk2. Kaldis P, Aleem E. Cell Cycle. 2005 Nov;4(11):1491-4. Epub 2005 Nov 29. Review. PMID: 16258277

Mathematical models of cell cycle regulation. Fuss H, Dubitzky W, Downes CS, Kurth MJ. Brief Bioinform. 2005 Jun;6(2):163-77. Review. PMID: 15975225

Plant Cell Cycle

Green light for the cell cycle. Inzé D. EMBO J. 2005 Feb 23;24(4):657-62. Epub 2005 Jan 27. Review. PMID: 15678103

Divide and die: cell cycle events as triggers of nerve cell death. Herrup K, Neve R, Ackerman SL, Copani A. J Neurosci. 2004 Oct 20;24(42):9232-9. Review. No abstract available. PMID: 15496657

Cytometry of the cell cycle: cycling through history. Darzynkiewicz Z, Crissman H, Jacobberger JW. Cytometry A. 2004 Mar;58(1):21-32. Review. No abstract available. PMID: 14994216

Bcl-2 in cell cycle regulation. Quinn LM, Richardson H. Cell Cycle. 2004 Jan;3(1):7-9. Review. No abstract available. PMID: 14657653

Open Access

Lighting the circle of life: fluorescent sensors for covert surveillance of the cell cycle. Thomas N. Cell Cycle. 2003 Nov-Dec;2(6):545-9. Review. PMID: 14504471

Cell Division Milestones Recent Nobel Prizes Binary Fission Prokaryotes And Eukaryote mitochondria Asexual reproduction replicates original cell to produce two identical cells Grow in numbers exponentially adequate nutrients and a fast life cycle single organism can multiply into billions High mutation rate of bacteria Movie: Embryo Mitosis Movie: Mitosis Animation Cell Cycle- Mitosis Cell Lifespan Body Cell Types About 210 types Lifespan Born Differentiate Function Die Cell Lifespan Body Cell Types About 210 types

Lifespan Born Differentiate Function Die Cell Lifespan Neutrophil 6-7 hours circulating 4 days in tissue Red blood cell 120 days Brain neuron, heart 50 - 100 years Lifespan Processes Birth Mitosis Except germ cells Meiosis Death Apoptosis Programmed cell death Necrosis Movie: Embryo Mitosis Movie: Cell Death (Apoptosis) Cell Cycle Mitosis (M phase) Cell birth(division) small time of cell cycle Interphase Most cell life Cell growth, function DNA synthesis organelle development Cell Cycle Time cell comes into existence until that cell divides again Rapidly growing human cells 20-24 hr Liver cells 1-2 year Neurons 1 only Quiescent G0 Cell Cycle- Stages Rapidly dividing cell 20-24hr Mitosis M 1 hr Interphase G1 Phase cellular growth 9hr Most variable time Can exit to G0 S Phase DNA duplication 9hr G2 Phase prepare for mitosis 4 hr Cell Cycle Differences Early embryonic cycle no growth occurs each daughter cell is half the size of parent cell cycle time is very short S phases and M phases alternate without any intervening G1 or G2 phases Cell Cycle Regulation Cell proliferation strictly regulated Cancer Unregulated/abnormal proliferation Cell Cycle- External Regulators External factors can also regulate progression through cycle Cell replacement in different tissues regulated by growth factors can be specific for specific cell types Growth Factor Model Fibroblasts in culture Serum- Proliferation Prepared by clotting Plasma- no proliferation Prepared by centrifugation (no clotting) Clotting allows platelets to release secretory granules Platelet-derived growth factor (PDGF) Connective tissue cells express PDGF receptors which bind the small PDGF glycoprotein Other Growth Factors Interleukin-2 (IL-2) Stimulates T lymphocytes Nerve Growth Factor (NGF) Promotes neuronal survival and growth Epidermal Growth Factor (EGF) Vascular Endothelial Growth Factor (VEGF) Insulin-like growth factors (IFG-1, IGF-2) Cell Cycle- Internal Regulators Cyclins Cyclically synthesized and degraded each cell cycle Cyclin-dependent Kinases Inactive until bound to a specific cyclin Cyclin-Dependent Kinases Drive M to S Phase cdk1 and cdk2 Cdk1 activated at G2 to M Cdk2 activated at G1 to S Cell Cyclins - Interphase Cell Cyclins - M Phase Division controlled by synthesis/degradation cyclin B regulatory subunit of Cdc2 protein kinase interphase cyclin B synthesis leads to formation of active cyclin B–Cdc2 complex induces entry into mitosis Rapid degradation of cyclin B leads to inactivation Cdc2 kinase Allow cell to exit mitosis and return to interphase next cell cycle