SC430 Molecular Cell Biology Welcome to Unit 8 Seminar with Dr Hall-Pogar Tonight we will discuss –Cell Cycle –I will be available at AIM:KaplanHallPogar before and throughout the seminar if you have any questions or issues. We will begin promptly at 8:00pmET

2 Unit Review DB No Project!

3 Overview: The Key Roles of Cell Division The ability of organisms to reproduce best distinguishes living things from non-living matter The continuity of life is based upon the reproduction of cells, or cell division Cell division is integral part of cell cycle

Types of cell division Prokaryotes –Binary fission Eukaryotes –Mitosis: Growth, development & repair Asexual reproduction (yields genetically identical cells) Occurs in somatic (body) cells –Meiosis: Sexual reproduction (yields genetically different cells with half the # of chromosomes) Occurs in specific reproductive cells Yields gametes (e.g., eggs & sperm) or spores

5 Cell Cycle The Cell’s Time Clock Smallest unit of life –all living things must reproduce Cells replicate for growth, replacement, and repair Cell division requires Mitosis & Cytokinesis Cytokinesis

6 Phases of the Cell Cycle The cell cycle consists of –Mitotic (M) phase (mitosis and cytokinesis) –Interphase (cell growth and copying of chromosomes in preparation for cell division) Interphase (about 90% of the cell cycle) can be divided into subphases: –G1 phase (“first gap”) –S phase (“synthesis”) –G2 phase (“second gap”)

G1G1 G2G2 S (DNA synthesis) INTERPHASE Cytokinesis MITOTIC (M) PHASE Mitosis

8 The Cell Cycle Control System The sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a clock The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received For many cells, the G1 checkpoint seems to be the most important one

G 1 checkpoint G1G1 S M M checkpoint G 2 checkpoint G2G2 Control system

G1G1 G 1 checkpoint G1G1 G0G0 If a cell receives a go-ahead signal at the G 1 checkpoint, the cell continues on in the cell cycle. If a cell does not receive a go-ahead signal at the G 1 checkpoint, the cell exits the cell cycle and goes into G 0, a nondividing state.

11 Cyclins & Cylin-Dependent Proteins Cyclin is a cytoplasmic protein that fluctuates in concentration Cyclin-Dependent Proteins: activate other proteins in the cell by phosphorylation (protein kinases)

12 What does MPF do?

Degraded cyclin G 2 checkpoint S M G2G2 G1G1 Cdk Cyclin is degraded MPF Cyclin Cdk Molecular mechanisms that help regulate the cell cycle accumulation Cyclin

14 Stop and Go Signs: Internal and External Signals at the Checkpoints An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase Some external signals are growth factors, proteins released by certain cells that stimulate other cells to divide For example, platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells in culture

15 Another example of external signals is density-dependent inhibition, in which crowded cells stop dividing Most animal cells also exhibit anchorage dependence, in which they must be attached to a substratum in order to divide

16 Cancer cells exhibit neither density- dependent inhibition nor anchorage dependence

Cells anchor to dish surface and divide (anchorage dependence). When cells have formed a complete single layer, they stop dividing (density-dependent inhibition). If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition). 25 µm Normal mammalian cells

Cancer cells do not exhibit anchorage dependence or density-dependent inhibition. Cancer cells 25 µm