Pre-Medicine Program - Cell Cycle

From CellBiology
Jump to: navigation, search
Pre-Medicine Links
Biology 1 - Cell Types | Biology 2 - Cell Compartments, Membranes | Biology 3-4 - Cell Export/Import | Biology 5 - Cell Cycle | Biology 7 - Cell Filament Systems | Biology 8 - Embryology | 2016 Note - These are the 2015 lecture links and some content provided/replaced by other lecturers for 2016.

Cell Cycle

The Cell Cycle in relation to cyclin levels

Introduction

Cell Cycle - "The time cell comes into existence until that cell divides again"

This lecture will introduce the cell cycle, which is the entire life of a cell from birth to death. You have already covered some concepts (Mitosis phase) in the Cell Division Lecture. Interphase is when a cell will carry out it's normal function in a tissue or organ. During this time gene expression and DNA duplication will occur in the nucleus and all of the processes I have described earlier in cell export and import will be occurring in the cytoplasm.

2012 - Diseases such as diabetes alters the proliferation (mitosis), functioning (interphase) and death (apoptosis) of cells in many different tissues. These diseases also affect the signaling and endocrine regulation of normal cell function.

Objectives

  • Understanding of the main stages of the cell cycle
  • Broad understanding of different cell lifespan
  • Brief understanding of the differences between embryonic and adult cell cycles
  • Brief understanding of the regulators of cell cycle
  • Broad understanding of cell death and abnormal cell cycles
Skin as an example of cell cycle.
Epidermis cartoon Cornified Epithelium

Prokaryote Division

Escherichia coli
  • Binary Fission - also seen in 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

Cell Lifespan

Blood Cells
  • Body Cell Types - about 210 types
  • Lifespan - Born, Differentiate, Function, Die or Divide

Cell Lifespan Examples

  • 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)
  • Growth - Expression of genes and proteins required to grow the cell, its organelles and cytoskeleton
  • Function - Expression of tissue specific genes and proteins
  • Division - DNA during cycle, whole cell in Mitosis
  • Death - Apoptosis (programmed cell death) Necrosis (un-programmed cell death)
Skin as an example of cell cycle.
Epidermis cartoon Cornified Epithelium

Cell Cycle Major Phases

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

Mitosis (M phase) - Cell birth(division), small time of cell cycle

Interphase - Most cell life: Cell growth, function, DNA synthesis, organelle development

Cell Cycle- Stages

Example of times in each stage for a rapidly dividing cell (20-24hr). Remember also that mitochondria have their own relatively independent cycle.

Mitosis Interphase
  • M phase 1 hr
  • divided into stages originally identified by light microscope.
  • covered in another of your lectures.
  • G1 Phase - cellular growth 9hr, Most variable time, can exit to G0
  • S Phase - DNA duplication 9hr
  • G2 Phase - growth prepare for mitosis 4 hr

Cell Cycle Differences

Early Embryonic Cycle

  • cycle time is very short, each daughter cell is half the size of parent cell
  • no growth occurs, S phases and M phases alternate without any intervening G1 or G2 phases

G0 Phase

  • exits the cycle at G1 (cancer cells do not enter G0)
  • cell can leave the cell cycle (temporarily or permanently)
  • temporarily - quiescent
  • permanently - terminally differentiated, cell will never reenter the cell cycle, carry out their function until they die
  • active repression of needed mitosis genes, not absence of signals for mitosis

Cell Cycle Regulation

Cyclins and Cyclin-Dependent Kinases need to interact for cell cycle progression
  • Cell proliferation is strictly regulated
  • Unregulated/abnormal proliferation is oncogenesis or Cancer

External Regulators

  • Cell replacement in different tissues regulated by growth factors (can be specific for specific cell types)
  • External factors can also regulate progression through cycle (primarily act on cells in G0 and G1)
  • The restriction point is the timepoint in G1 when cells no longer respond to withdrawal of growth factors by returning to G0, but progress to S phase.

Internal Regulators

  • 1980s - studies in Xenopus eggs and starfish oocytes
  • purified M phase-promoting factor (MPF, cyclin B and CDC2 also called cyclin-dependent kinase)
  • Cyclins are proteins synthesized and degraded each cell cycle (hence the name).

Regulator Checkpoints

  • These regulators are often described as "tumor suppressor proteins" due to their ability to block tumor (cancer) growth.
  • Conversely, mutations in these genes often lead to tumor growth. (p53 levels are low through a continuous degradation)


Links: An overview of the cell-cycle control system | Cyclins and Cyclin-Dependent Kinases | Checkpoints in the cell-cycle control system | How DNA damage arrests the cell cycle in G1

Cell Death

Below are two electron microscope images of the same cell type (neuron) dying by either necrosis or apotosis Neuron necrosis apoptosis.jpg

Apoptosis - genetic errors
Apoptosis - macrophage

Necrosis

  • Greek, nekros = corpse
  • pathological cell death from extrinsic injury (tissue damage)
  • autoimmune insulin-dependent diabetes?
  • irreversible

Apoptosis

Greek, ptosis = falling, as in when leaves fall from a tree in autumn.

Many signals induce apoptosis:

Process required for:

  • Embryogenesis
  • Metamorphosis
  • Endocrine dependent tissue atrophy
  • Normal tissue turnover
  • Variety of pathologic conditions

Selective process for deletion of cells:

  • Superfluous
  • Infected
  • genetic errors
  • transformed cells

Cornification

Cornified envelope - formation or ‘keratinization’ is specific of the skin to create a barrier function. Although apoptosis can be induced by injury in the basal epidermal layer (e.g., UV irradiation), cornification is exclusive of the upper layers (granular layer and stratum corneum).

  • Cell death seen in skin - eliminate cytoplasmic organelles, modify plasma membrane
  • Lipids - accumulate lipids in keratohyalin granules (stratum granulosum), extrude lipids to the extracellular space, desquamation (loss of corneocytes)

Oncogenesis

Cancer requires multiple mutations.png Oncogenesis (carcinogenesis or tumorigenesis) is the cellular process commonly called "Cancer".


There are many detailed resources on oncogenesis (cancer) this is only a brief mention in regard to cell cycle (See also the tumor suppressor section above).

An important issue is the concept of "multiple hits" in this process.


Viruses some viruses can infect human cells and lead to oncogenesis

  • cervical cancer, liver cancer, and certain lymphomas, leukemias, and sarcomas
  • for example - human papillomavirus (HPV) (cervical cancer)

References

Science Lectures: Cell Cycle | Cell Division | Cell Death 1 | Cell Death 2

Christine M Kusminski, Shoba Shetty, Lelio Orci, Roger H Unger, Philipp E Scherer Diabetes and apoptosis: lipotoxicity. Apoptosis: 2009, 14(12);1484-95 PubMed 19421860