Lecture 13, Chapter 11 (Dr. Bittel Study Guide) Flashcards
How does supercoiling arise? What is the difference between positive and negative supercoiling?
Supercoiling arises from topoisomerases catalyzing the overwinding (positive supercoiling) or underwinding (negative supercoiling) of the DNA double helix. Supercoiling may occur:
- when the DNA molecule does not have free ends, as in circuluar DNA molecules, or
- when the ends of the DNA molecule are bound to proteins that prevent them from rotating about each other, as in linear eukaryotic chromosomes
What functions does supercoiling serve for the cell?
Supercoiling compacts the DNA. Negative supercoiling helps to unwind the DNA duplex for replication and transcription
Describe the composition and structure of the nucleosome
The nucleosome core particle contains two molecules each of histones H2A, H2B, H3 and H4 which form a protein core with 145-147 base pairs of DNA wound around the core. Chromatosomes contain the nucelosome core with a molecule of histone H1
What are epigenetic changes and how are they brought about?
Epigenetic chang3es are changes in gene expression that are passed on to cells or future generations, but do not involve alteration of the nucleotide sequence. Epigenetic changes are brought about by altering DNA structure, such as methylation of the DNA, or altering chromatin structure by modifying histones
Describe the function of the centromere. How are centromeres different from other regions of the chromosome?
Centromeres are the points at which the spindle fibers attach to the chromosome. They are necessary for proper segregation of the chromosomes in mitosis and meiosis. Most eukaryotic centromeres are characterized by heterochromatin consisting of highly repetitive DNA. Centromeres are thought to exist at specific locations on the chromosome because of epigenetic changes to chromatin structure at those locations. For example, nucleosomes at centromeres often possess the variant histone CenH3. This special chromatin structure promotes the formation of the kinetochore, to which spindle fibers attach
Describe the function and molecular structure of a telomere
Telomeres are the ends of the linear chromosomes in eukaryotes. They cap and stabalize the ends of the chromosomes to prevent degradation by exonuclease or joining of the ends. Telomeres also enable replication of the ends of the chromosomes by an enzyme called telomerase. Telomeric DNA sequences consist of repeats of a simple sequence, usually in the form of 5’C (A/T)
What is the difference between euchromatin and heterochromatin?
Euchromatin undergoes regular cycles of condensation during mitosis and decondensation during interphase, whereas heterochromatin remains highly condensed throughout the cell cycle, except transiently during replication. Nearly all transcription takes place in euchromatic regions, with little or no transcription within heterochromatin. (248 chapter 11: chromosome structure and organelle DNA??)
What is the C value of an organism?
The C value is the amount of DNA per cell of an organism
Describe the different classes of DNA sequence variation that exist in eukaryotes
Unique-sequence DNA, present in only one or a few copies per haploid genome, represents most of the protein coding sequences, plus a great deal of sequences with unknown function.
Moderately repetitive sequences, a few hundred to a few thousand base pairs long, are present in up to several thousand copies per haploid genome. Some moderately repetitive DNA sequences consist of functional genes that code for rRNAs and tRNAs, but most are made up of transposable elements and remnants of transposable elements.
Highly repetitive DNA, or satellite DNA, consists of clusters of tandem repeats of short (often less than 10 base pairs) sequences present in hundreds of thousands to millions of copies per haploid genome
Introduction to chapter discussed a study of telomere length in Romanian children. The study demonstrated that children raised in orphanages had shorter telomeres than children raised in foster homes. What effect, if any, do you think having shorter telomeres in childhood might have on adult life?
Somatic cells do not normally express telomerase, so their telomeres often shorten with every cell division. People whose telomeres are already shorter in childhood may have reduced replicative lifespans for their somatic cells, leading to earlier aging for the immune system and cells and organs that the body needs to replenish continually, such as skin cells, intestinal cells, and blood cells. They may experience symptoms of aging earlier, and have shorter life expectancies.
Based on the DNA sensitivity to DNAase I illustrated in Figure 11.7, which type of chicken hemoglobin (embryonic or adult) is likely produced in highest quantity at the following tissues and developmental stages?
a. Erythroblasts during the first 24 hours
b. Erythroblasts at day 5
c. Erythroblasts at day 14
d. Brain cells throughout development
a. None-neither the embryonic nor adult hemoglobin genes show DNAase I
b. the embryonic hemoglobin gene but not the adult genes, shows DNAase I sensitivity, indicating an open chromatin conformation that is conducive for transcription
c. Adult–now the adult hemoglobin genes show DNAase I sensitivity, but the embryonic gene is DNAase I is insensitive
d. None–neither embryonic nor adult hemoglobin genes show DNAase I sensitivity in brain cells at any time of development
Would you expect to see more or less methylation in regions of DNA that are sensitive to digestion by DNAase I? Why?
Less methylation. Regions of DNAase I sensitivity are less condensed than DNA that is not sensitive to DNAase I, the sensitive DNA is less tightly associated with nucleosomes, and it is in a more open state. Open states can represent areas of euchromatin which are undergoing DNA repair and/or transcription. Such a state is associated with less methylation.
Suppose a chemist develops a new drug that neutralizes the positive charges on the tails of histone proteins. What would be the most likely effect of this new drug on chromatin sturcture? Would this drug have any effect on gene expression? Explain your answers.
Such a drug would disrupt the ionic interactions between the histone tails and the phosphate backbone of DNA and thereby cause a loosening of the DNA from the nucleosome. The drug may mimic the effects of histone acetylation, which neutralizes the positively charged lysine residues. Changes in chromatin structure would result from the altered nucleosome-DNA packing and possible changes in interaction with other chromatin modifying enzymes and proteins. Changes in transcription would result because DNA may be more accessible to transcription factors
