Chromosome structures Telomeres are: Repetitive DNA sequences at the ends of all human chromosomes They contain thousands of repeats of the six-nucleotide sequence, TTAGGG In humans there are 46 chromosomes and thus 92 telomeres (one at each end)
Ends of linear chromosomes Telomeres Ends of linear chromosomes Centromere Telomere Telomere Repetitive DNA sequence (TTAGGG in vertebrates) Specialized proteins Form a 'capped' end structure
What do telomeres do? They protect the chromosomes. They separate one chromosome from another in the DNA sequence Without telomeres, the ends of the chromosomes would be "repaired", leading to chromosome fusion and massive genomic instability. Telomeres are also thought to be the "clock" that regulates how many times an individual cell can divide. Telomeric sequences shorten each time the DNA replicates.
What is telomerase Telomerase (TEE-LÓM-ER-ACE) is a ribonucleoprotein enzyme complex (a cellular reverse transcriptase) that has been referred to as a cellular immortalizing enzyme. It stabilizes telomere length by adding hexameric (TTAGGG) repeats onto the telomeric ends of the chromosomes, thus compensating for the erosion of telomeres that occurs in its absence.
How Does Telomerase Work? Telomerase works by adding back telomeric DNA to the ends of chromosomes, thus compensating for the loss of telomeres that normally occurs as cells divide. Most normal cells do not have this enzyme and thus they lose telomeres with each division. In humans, telomerase is active in germ cells, in vitro immortalized cells, the vast majority of cancer cells and, possibly, in some stem cells. High telomerase activity exists in germ cells, stem cells, epidermal skin cells, follicular hair cells, and cancer cells.
Research also shows that the counter that controls the wasting away of the telomere can be "turned on" and "turned off". The control button appears to be an enzyme called telomerase which can rejuvenate the telomere and allow the cell to divide endlessly. Most cells of the body contain telomerase but it is in the "off" position so that the cell is mortal and eventually dies. Some cells are immortal because their telomerase is switched on Examples of immortal cells: blood cells and cancer cells Cancer cells do not age because they produce telomerase, which keeps the telomere intact.
Where are the genes located? Genes are located on the chromosomes. Every species has a different number of chromosomes. There are two types of chromosomes: autosomes and sex chromosomes
Definitions of the gene The gene is to genetics what the atom is to chemistry. The gene is the unit of genetic information that controls a specific aspect of the phenotype. The gene is the unit of genetic information that specifies the synthesis of one polypeptide.
Eukaryotic Gene Structure 5’ - Promoter Exon1 Intron1 Exon2 Terminator – 3’ UTR splice splice UTR transcription Poly A translation protein
Promoter Promoter determines: Which strand will serve as a template. Transcription starting point. Strength of polymerase binding. Frequency of polymerase binding.
Prokaryotic Promoter One type of RNA polymerase. Pribnow box located at –10 (6-7bp) –35 sequence located at -35 (6bp)
Eukaryote Promoter 3 types of RNA polymerases are employed in transcription of genes: RNA polymerase I transcribes rRNA RNA polymerase II transcribes all genes coding for polypeptides RNA polymerase III transcribes small cytoplasmatic RNA, such as tRNA.
Promoters sequences can vary tremendously. RNA polymerase recognizes hundreds of different promoters
Strong promoter resemble the consensus sequence. Mutations at promoter sites can influence transcription. Human gene Beta globin
Termination Sites The newly synthesized mRNA forms a stem and loop structure (lollipop). A disassociation signal at the end of the gene that stops elongating and releases RNA polymerase. All terminators (eukaryotes and prokaryotes) form a secondary structure.
Exons, Introns, and Genes The human genome: 23 pairs of chromosomes 2.9 billion A’s, T’s, C’s, G’s ~22,000 genes (?) ~1.4% of genome is coding
Splicing of Eukaryotic mRNA’s After transcription by the polymerase, eukaryotic pre-mRNA’s are subject to splicing by the spliceosome, which removes introns: pre-mRNA exon exon intron mature mRNA discarded intron
Types of Exons Three types of exons are defined, for convenience: initial exons extend from a start codon to the first donor site; internal exons extend from one acceptor site to the next donor site; final exons extend from the last acceptor site to the stop codon; single exons (which occur only in intronless genes) extend from the start codon to the stop codon: