Chromatin the stuff 'inside of' the nucleus is...  DNA: Complexed with histone proteins & acidic nuclear proteins heterochromatin (condensed & inactive - dark in EM's) euchromatin: (less dense & active - greyish in EM's)

Chromosome Strucutre

Formation of Chromosomes DNAi_packaging_vo2-sm.wmvhttp:// DNAi_packaging_vo2-sm.wmv

DNA CODE DNA codes for genes Genes are series of nucleotides, together code for amino acids –Amino acids make up proteins –Proteins help to regulate metabolic functions and build cellular structures One Gene One Protein –Each gene codes for a specific protein

Protein Synthesis Gene →Protein –Transcription: Copying down the genetic code –Translation: Converting the code into a Protein –DNA → RNA → PROTEIN

Transcription DNA: Segments of DNA code for a gene –The segment is copied by RNA –This is called messenger RNA The mRNA is modified Non coding sections are removed Coding sections are stuck together DNA STRAND mRNA STRAND

Translation mRNA moves from the nucleus to the cytoplasm mRNA docks onto a Ribosome The ribosome reads the mRNA code and the protein is built

Translation tRNA molecules exist in the cytoplasm They escort amino acids to the ribosome where they are matched up to the mRNA strand The transfers RNAs dock onto the mRNA The amino acids they are carrying line up and bond together.

A Closer look at Transcription Within the DNA strand (gene) there are non coding areas. –When the m RNA copies the DNA it copies all of it. –The non coding areas (introns) have to taken out before it can leave the nucleus

The coding sections (exons) are stuck back together. The exons are what leaves the nucleus and travels to the ribosome.

1.DNA in a nucleus 2.Genes have introns 3.mRNA has transcripts of only 1 gene 4.mRNA must be fully formed in nucleus before being translated in cytoplasm 5.mRNA is modified, introns are cut out. 6.A cap is added to the 5’ end of the mRNA and a tail of 200 repeating A nucleotides is added to the end. 7.Translation begins by the cap binding to the ribosomal unit 8.Ribosomes are bigger Transcription in Eukaryotic Cells

Prokaryotic cells 1.Circular DNA in cytoplasm 2.No introns 3.mRNA transcript has several genes 4.mRNA can be transcribed and translated simultaneously in cytoplasm 5.There are no introns 6.No cap but a small nucleotide sequence is the lead segment 7.Transcription begins using a star sequence of AUG.

Control of gene Expression Types of control in Eukaryotes

Transcriptional - These mechanisms prevent transcription. Posttranscriptional - These mechanisms control or regulate mRNA after it has been produced. Translational - These mechanisms prevent translation. They often involve protein factors needed for translation.

Transcriptional Control These mechanisms prevent mRNA from being synthesized. –Heterochromatin and Euchromatin –Heterochromatin is tightly wound DNA and visible during interphase. It is inactive because DNA cannot be transcribed while it is tightly wound. –Euchromatin is not tightly wound. It is active. –Example: Barr body One X chromosome is inactivated in females by producing a tightly-wound structure called a Barr body. –Example: Calico cats: female have two X chromosomes hair color yellow or black are located on those chromoses. At the time of embryo development (64 cells) one of the X chromosomes in each cell turns off. Daughter cells from those original 64 cells all have the same X chromosome turned off. This gives Cailco cats there patchy hair coloring. Found only in females

Regulatory Proteins and Transcription Proteins called transcription factors function by binding to the promoter and to another region called the enhancer. The enhancer region may be located at a distance from the gene. These transcription factors are necessary for RNA polymerase to attach. Transcription begins when the factors at the promoter region bind with the factors at the enhancer region creating a loop in the DNA.

In the diagram below, transcription factors are represented by the rectangle and the oval.

Regulatory Proteins and Transcription Hundreds of different transcription factors have been discovered; each recognizes and binds with a specific nucleotide sequence in the DNA. A specific combination of transcription factors is necessary to activate a gene. Transcription factors are regulated by signals produced from other molecules. For example, hormones activate transcription factors and thus enable transcription. Hormones therefore activate certain genes.

Posttranscriptional Control These mechanisms control or regulate mRNA after it has been produced. Differential Removal of Introns This can produce variations in the mRNA produced. Different mRNA may have different introns removed. Differential removal of introns enables a gene to code for more than one different protein. An average human gene is thought to code for 3 different proteins. For example, experiments using radioactive labeling show that calcitonin produced by the hypothalamus is different from that produced by the thyroid. In each case, the same gene produces the protein.

Differential Removal of Introns

Speed of Transport of mRNA Through the Nuclear Pores –Evidence suggests that this time may vary. Longevity of mRNA –Messenger RNA can last a long time. For example, mammalian red blood cells eject their nucleus but continue to synthesize hemoglobin for several months. This indicates that mRNA is available to produce the protein even though the DNA is gone. Posttranscriptional Control

Ribonucleases Ribonucleases are enzymes that destroy mRNA. Messenger RNA has noncoding( cap and tail) nucleotides at either end of the molecule. These segments contain information about the number of times mRNA is transcribed before being destroyed by ribonucleases. Hormones stabilize certain mRNA transcripts.

Translational Control These mechanisms prevent the synthesis of protein. They often involve protein factors needed for translation. Preventing Ribosomes From Attaching –Proteins that bind to specific sequences in the mRNA and prevent ribosomes from attaching can prevent translation of certain mRNA molecules. Initiation Factors –Initiation factors are proteins that enable ribosomes to attach to mRNA. These factors can be produced when certain proteins are needed. For example, the eggs of many organisms contain mRNA that is not needed until after fertilization. At this time, an initiation factor is activated.

Posttranslational Control These mechanisms act after the protein has been produced. Protein Activation –Some proteins are not active when they are first formed. They must undergo modification such as folding, enzymatic cleavage, or bond formation. Example: Bovine proinsulin is a precursor to the hormone insulin. It must be cleaved into 2 polypeptide chains and about 30 amino acids must be removed to form insulin. Feedback Control –Some enzymes in a metabolic pathway may be negatively inhibited by products of the pathway.

Gene Expression in Prokaryotic Cells Prokaryotes have two levels of gene control. Transcriptional mechanisms control the synthesis of mRNA Translational mechanisms control the synthesis of protein after mRNA has been produced.

Operons Operons are groups of genes that function to produce proteins needed by the cell. There are two different kinds of genes in operons: –Structural genes code for proteins needed for the normal operation of the cell. For example, they may be proteins needed for the breakdown of sugars. The structural genes are grouped together and a single mRNA molecule is produced during their transcription. –Regulator genes code for proteins that regulate other genes. Operons have not been found in eukaryotes

The lac operon Lactose is a sugar found in milk. If lactose is present, E. coli (the common intestinal bacterium) needs to produce the necessary enzymes to digest it. Three different enzymes are needed. In the diagrams below, genes A, B, and C represent the genes whose products are necessary to digest lactose. In the normal condition, the genes do not function because a repressor protein is active and bound to the DNA preventing transcription. When the repressor protein is bound to the DNA, RNA polymerase cannot bind to the DNA. The protein must be removed before the genes can be transcribed.

The repressor protein is produced by a regulator gene. The region of DNA where the repressor protein binds is the operator site. The promoter site is a region of DNA where RNA polymerase can bind. The entire unit (promoter, operator, and genes) is an operon.

Example of Translational Control in Prokaryotes: Antisense RNA Normally, mRNA is synthesized off of the template (antisense) strand of DNA. Antisense RNA is synthesized from the noncoding (sense) strand of DNA. The two mRNA molecules bond together, inactivating the mRNA. This mechanism appears to be universal among bacteria.

Differentiation in Eukaryotes Differentiation when cell of a multi-cellular organisms develop into specific cells. Each cell has the entire genome, but only uses a specific portion of it, based on the structure and function of the cell. –Liver cells specialize in breaking down fat while muscle cells focus on motion. Genes control the development of the cells in a newly forming organism.

HOMEOTIC GENES Homeotic genes: regulatory genes that determine where appendages go and development of them. Homeobox: a specific DNA sequence within a homeotic gene that regulates patterns of development. These genes are the masters of development. They determine body organization. Homeotic sequences are in all organisms and we share the similar homeobox sequences between species.

HOMEOTIC GENES

CANCER An abnormal growth of cells Tumors: masses of cells that replicate at an abnormally high rate. –benign: fibroid types of cysts, or warts that stay in a local area and reproduce. –malignant tumors that leave their area and invade healthy tissue.

Normal cell cycle In our body cell division is always occurring to repair replace worn out cells. Proto oncogenes: Genes that control this in a specific and precise manner. 3 types 1.induce cell proliferation. 2.anti oncogenes:inhibit cell proliferation 3.surpresses or trigger programmed cell death. This keeps normal body cells from dying before their time Controls of the cell cycle are extensive and diverse. If any of these mechanisms are altered due to a gene mutation then cancer is a possible outcome.

CANCER Oncogenes: mutation in proto-oncogens resulting in uncontrolled cell division All cancer cells have several common characteristics membranes change cytoskeleton shrinks amplified reliance on glycolysis. Cells grow and divide abnormally. Overcrowding in tissue occurs increase in small blood vessels that serve the growing mass. Cancer cells are more able to move from original location. They are not as adhesive as their original tissue type was. This leads to establishing distant tumors they are lethal, unless eradicated they lead to the death of the organism.

Causes Can occur spontaneously Can be accelerated by chemicals known as carciogens Viruses Genetic pre-dispostion: you have a few of the mutations in your genes that can lead to cancer

Prevention Healthy living –Balanced diet –Exercise –Avoid known carcinogens –Regular checkups –Reduced stress