Course in Molecular Biology Leuven, October – November 2002 Program Basics of molecular biology Transcription Translation Regulatory pathways DNA and diseases Biotechnology

Lesson 1: Basics of molecular biology I. The Cell’s Organization II. Cell Cycle and Cell Division III. Cellular Molecules IV. The Genetic Dogma

The Cell’s Organization

All organisms: 1 or more cells EUKARYOTES PROKARYOTES

The animal cell

A plant cell

A bacterium

The Main Functions of the Membrane-bounded Compartments of a Eukaryotic Cell Compartment Main Function Cytosol contains many metabolic pathways protein synthesis Nucleus contains main genome DNA and RNA synthesis Endoplasmic reticulum (ER) synthesis of most lipids synthesis of proteins for distribution to many organelles and plasma membrane Golgi apparatus modification, sorting, and packaging of proteins and lipids for either secretion or delivery to another organelle Lysosomes intracellular degradation Endosomes sorting of endocytosed material Mitochondria ATP synthesis by oxidative phosphorylation Chloroplasts (in plant cells) ATP synthesis and carbon fixation by photosynthesis Peroxisomes oxidation of toxic molecules

Compartimentation of the eukaryote cell: various organelles

Cell nucleus Contains genetic information: DNA Nucleolus: Ribosome building machine Protein factories in the cytoplasm

Each human cell contains 46 chromosomes (except sperm or egg cells)

in a cell that is about to divide Chromosomes in a cell that is about to divide

Mitochondria: factories of energy glucose O2 Pi ADP ATP H2O CO2

The endoplasmic reticulum smooth (metabolism+synthesis of lipids) rough (protein synthesis)

The Golgi apparatus cis trans medial  processing of secretory proteins  sorting cellular proteins

Inside the cytosol: the cytoskeleton “microtubules” maintainance of cell shape and mobility ancor for other cellular structures

Presentation: DNA

Cell Cycle and Cell Division

Some Eukaryotic Cell-Cycle Times Cell Type Cell-Cycle Times Early frog embryo cells 30 minutes Yeast cells 1.5-3 hours Intestinal epithelial cells about 12 hours Mammalian fibroblasts in culture about 20 hours Human liver cells about 1 year

The eukaryotic cell cycle

Separation of sister chromatides during mitosis (mitosis = normal cell division)

assist chromosomes during cell division (mitosis) Microtubuli: assist chromosomes during cell division (mitosis)

Different stages of the M phase during cell division (mitosis)

The three DNA sequence elements needed to produce a eukaryotic chromosome that can be replicated and then segregated at mitosis

Kinetochores and kinetochore microtubules

Gametogenesis: meiosis (= specialized form of cell division giving rise to sperm and egg cells) Meiosis I

Meiosis I (continued) Meiosis II  Haploid cell Cell division without DNA replication  Haploid cell

Chromosomes, mitosis and meiosis Presentation: Chromosomes, mitosis and meiosis

Cellular Molecules

The four main families of small organic molecules in cells

Macromolecules are abundant in cells

The general reaction by which a macromolecule is made Condensation reaction: H2O molecule is released

The four main families of small organic molecules in cells

Glucose, a simple sugar

Monosaccharides

Sugar ring formation in aqueous solution

formed by two sugar monomers Disaccharides: formed by two sugar monomers

Oligo- and polysaccharides

Complex oligosaccharides

The four main families of small organic molecules in cells

Phospholipid structure and orientation of phospholipids in membranes

The four main families of small organic molecules in cells

A simple amino acid: alanine

A small part of a large protein molecule

The four main families of small organic molecules in cells

the energy carrier in cells ATP: the energy carrier in cells

Various functions of proteins

Proteins as polypeptide chains

Three types of noncovalent bonds that help proteins fold

The size of proteins

Several levels of protein organization

Many protein molecules contain multiple copies of a single protein subunit

Proteins often have highly specific binding sites

How a set of enzyme-catalyzed reactions generates a metabolic pathway

Phosphorylation and ATP hydrolysis drive protein functions

Genetic information is stored in the DNA

DNA and its building blocks

DNA has an orientation

DNA encodes proteins

“Genes” encode proteins

DNA replication

DNA synthesis and proofreading

Replication of eukaryotic chromosomes

The replication fork in detail

DNA replication can cause mutations

DNA repair

possible cause of diseases and disfunctionalities Mutations: possible cause of diseases and disfunctionalities

The Genetic Dogma

From DNA to protein

Transcription by RNA polymerase

RNA vs DNA mRNAs codes for proteins rRNAs forms part of the structure of the ribosome and participates in protein synthesis tRNAs used in protein synthesis as an adaptor between mRNA and amino acids Small RNAs used in pre-mRNA splicing, transport of proteins to ER, and other cellular processes

Genes contain introns and exons

Heredity and inheritance Presentation: Heredity and inheritance