Chapter Four Essays
1) What are the striking features of the human genome?
- a. Little of it codes for proteins. Much of the remaining DNA is made up of short, mobile pieces of DNA that have gradually inserted themselves in the chromosome over evolutionary time.
- b. It’s large average gene size of 27,000 nucleotide pairs. Only about 1300 nucleotide pairs are required to encode a protein of average size. The rest of the DNA in a gene has long stretches of noncoding DNA (introns). Aside from eons and intron, there are also regulatory DNA sequences, which are also responsible for ensuring that th gene is turned on or off at the proper time, expressed at the appropriate level, and only in the proper type of cell.
- c. The critical information needed to produce a human seems to be in an alarming state of disarray
1) What are the three type of specialized nucleotide sequences in DNA?
- a. Replication origin: location at which duplication of DNA begins; several are located on chromosomes
- b. Centromere: allows one copy of each duplicated and condensed chromosome to be pulled into each daughter cell when a cell divides ; kinetochore form at the centromere and attach the chromosomes to the mitotic spindle, allowing them to be pulled apart
- c. Telomeres: the ends of a chromosome; contain repeated nucleotide sequences that enable the ends to be efficiently replicated; also form structures that protect the end of the chromosome from being mistaken by the cell for a broken DNA molecule in need of repair
1) How are the chromosome packaged?
a. Specific regions of interphase chromosomes decondense as the cells gain access to specific DNA sequence for gene expression, DNA repair, and replication—and then recondense when these processe are completed. The packaging of chromosome is accomplished in a way that allows rapid localized, on-demand access to the DNA
1) How were nucleosomes determined?
a. They were determined after first isolating them from unfolded chromatin by digestion with particular enzymes (called nucleases) that break down DNA by cutting between the nucleosomes. After digestion for a short period, the exposed DNA between the nucleosome core particles, the linker DNA, is degraded.
1) What is the structure of a nucleosome core particle?
- a. It is a disc-shaped histone core around which DNA is tightly wrapped in a left-handed coil. The histones share a structural motif, called the histone fold, formed from three alpha helices connected by two loops
- b. The histone folds first bind to each other to form H3-H4 and H2A-H2B dimers, and the the H3-H4 dimers combine to form tetramers. An H3-H4 tetramer then furthers combines with two H2A-H2B dimers to form the compact octamer core, around which the DNA is wound
- c. The interface between DNA and histone is extensive: hydrogen bonds between DNA and the histone core in each nucleosome. Hydrophobic interactions and salt linkages also hold it together
1) How is DNA wound around the histone?
- a. It is not smooth; rather, several inks are seen in the DNA. The bending requires a substantial compression of the minor groove of the DNA helix. Certain dinucleotides in the minor groove are easy to compress, and some nucleotide sequences bind the nucleosome more tightly than others.
- b. In addition to its histone fold, each of the core histones has an N-terminal amino acid tail, which extends out from the DNA-histone core. These histone tails are subject to several different types of covalent modifications that in turn control critical aspects of chromatin structure and function
1) How is DNA accessed on nucleosomes?
- a. DNA in an isolated nucleosome unwraps briefly from each end before the partially unwrapped structure recloses.
- b. There are also ATP-dependent chromatin remodeling complexes, which contain subunits that hydrolyze ATP and bind to both the protein core of the nucleosome and to the double-stranded DNA that winds around it. The structure of the nucleosome is changed temporarily, making the DNA less tightly bound to the histone core.
- c. Through repeated cycle of ATP hydrolysis, the remodeling complexes can catalyze nucleosome sliding; and, with help from histone chaperone (negatively charged proteins), some remodeling complexes can remove either all or part of the nucleosome core from a nucleosome—catalyzing either an exchange of its H2A-H2B histones, or the complete removal of the octameric core from the DNA
1) How are ATP-dependent chromatin remodeling complexes controlled?
a. As genes are turned on and off, chromatin remodeling compelxes are brought to specific regions of DNA where they act locally to influence chromatin structure
1) What is the most important influence on nucleosome positioning?
a. It appears to be the presence of other tightly bound proteins on the DNA. Some bound proteins favor the formation of a nucleosome adjacent to them. Others create obstacles that force the nucleosomes to move to positions between them.
1) What cause nucleosomes to stack so tightly on one another?
a. The nucleosome to nucleosome linkages formed by histone tails, the histone H1, which links histones
- a. They are reversible. Lysines can be methylated or acetylated by enzyme that are recruited to specific sites on the chromatin at different times in each cell’s life history. The recruitment depends on gene regulatory proteins that bind to specific DNA sequences along chromosome. Covalent modifications can persist long after gen regulatory proteins that induced them have disappeared.
- i. Acetylation of lysines on the N-terminal tails loosens chromatin structure because adding an acetyl goup to lysine removes its positive charge, reducing its affinity for adjacent nucleosome.
- b. Modifications also allow specific proteins to be attracted to the proteins
1) Explain the code reader complex.
a. It is compiled of different modules that have different functions and altogether to execute an appropriate biological function. It has protein modules binding to specific histone modifications on nucleosomes bound to a scaffold protein. The complex then binds to a covalent modification on a histone tail, causing a protein complex with catalytic activities and additional binding sites to come and induce gene expression, gene silencing, or other biological functions.
1) Explain the code-reader-writer complex.
a. The code writer is an enzyme that creates a specific modification on one or more of the four nucleosomal histones. This mark is recognized by a code reader, which binds tightly to the nucleosome. After its recruitment to a specific site on a chromosome by a gene regulatory protein, the writer collaborates with a code-reader protein to spread its mark from nucleosome to nucleosome by means of the indicated reader-writer complex. The reader and writer must recognize the same histone modification mark.
1) What are the reasons for compaction of chromosomes during mitosis?
- a. First, when condensation is complete (in metaphase), sister chromatids have been disentangled from each other and lie side by side. Thus, the sister chromatids can easily separate when the mitotic apparatus begins pulling them apart.
- b. Second, the compaction of chromosomes protects the relatively fragile DNA molecules from being broken as they are pulled to separate daughter cells
- c. Condensation begins early in M phase.
1) Why are introns important?
a. Within them, there would be only a few sites in the original gene at which a recombinational exchange between DNA molecules could duplicate a domain.