Lecture 4 Reading.docx

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18 Apr 2012
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Lecture 4 Reading
Chapter 4; pp.202- 206
Eucaryotic DNA is Packaged into a set of chromosomes
- human genome, 3.2X109 nucleotides is distributed into 24 different
chromosomes
- each chromosome consists of a single long linear DNA molecule associated
with protein that folds it
- The protein and the DNA collectively is called the chromatin
- Cells are homologous as they contain two copies of each chromosome
- non homologs in sex cells strictly.
- XX in females and XY in males.
- Human karyotype is the 46 human chromosomes being displayed at mitosis
Bacteria
-carry genes on a single DNA molecule. It is circular
-bacterial chromosome different in structure than that of the eukaryote
chromosomes. Very little is known on packaging as well.
Chromosomes contain long string of genes
-Genes on chromosomes make specific proteins and some genes make RNA as the
final product. These RNA act as catalysts etc..
-Complexity and number of genes is true. However humans have less genes then
some bacteria so it shows that having less DNA is no handicap
- junk DNA in humans
The nucleotide sequence of the human genome shows how are genes are arranged
- human genome project showed that little of genome codes for protein
- most of DNA is made up of short pieces of DNA inserted over evolution
“transposable elements”
- average gene size is 27,000 nucleotides. THAT’S BIG. Only 13,000 needed for
the protein. Rest noncoding
- coding region called exons, noncoding called introns.
- Each gene is also associated with regulatory DNA sequences, ensuring that
genes are turned on or off at the right time, to the right extent and in the right
cells
pp. 208-218
Chromosomes exist in different states throughout the life of a cell
Mitosis ensures that dna is portioned and sent
- interphase is pre step to mitosis; In interphase, chromosomes are replicated
- mitosis’ chromosomes become highly condensed and then are separated,
distributed to two daughter cells.
- This condensed chromosome in mitosis is called mitotic chromosomes.
Chromosomes most easily visualized .
- Interphase chromosomes are long threads in nucleus, before mitosis
Each DNA molecule that forms linear chromosomes must contains a centromere,
two telomeres and replication origins
-3 specialized nucleotide sequences help basic function of cells
1. replication origin: location where duplication of DNA begins
2. centromere: allows one copy of each duplicated and condensed chromosome to
be pulled into each daughter cell after division. Protein complex called kinetochore
forms at centromere and attaches the duplicated chromosome to each mitotic
spindle to allow them to be pulled apart
3. telomeres: ends of chromosomes, contain repeated nucleotides that enable ends
of chromosomes to be replicated easily. Also forms structures that protect end of
chromosome from being seen by cell as broken DNA in need of repair
DNA molecules highly condensed in chromosomes
- Chromosome structure is dynamic
- DNA packaging is done in manner that allows for rapid localization and on
demand access to DNA
Nucleosome are a basic unit of Eucaryotic chromosome structure
-proteins that bind to DNA to form chromosomes are composed of two groups:
1) Histones- a lot of it. Responsible for most basic level of chromosome packing-
nucleosome
2) nonhistones
- collectively they are now as chromatin
Nucleosome:
- Is a level of chromosome packing
- made by histones
- protein DNA complex
1) Histones chromosomal proteins
- Responsible for the first and most basic level of chromosome packing- the
nucleosome(protein DNA complex) is packed by histones.
- if we look at nuclei in interphase, and then focus on chromatin, we see it composed
of something resembling beads on string. The string is DNA, and each bead is a
nucleosome, which consists of DNA wound around histone protein core.
4 histone proteins + DNA= nucleosome
6 Nucleosomes added up= chromatin
-Nucleosomes repeat every 200 nucleotide pairs.
-Formation of nucleosomes converts DNA moleculeschromatin thread one third
its original size.
2) nonhistone chromosomal proteins.
The structure of the nucleosome core particle reveals how DNA is packaged
- all histones share structural motif called histone fold
Assembly of nucleosome occurs by: histone folds(H4+H3, & H2A+H2B) binds to
each other to form H3-H4 and H2A-H2b dimers. H3-H4 dimers combine and =
H3-H4 tetramers. A H3-H4 tetramer combines with two H2A-H2b dimers to make
octamer core
-142 hydrogen bonds formed between DNA and histone in each nucleosome
- nearly half if these bonds form between the amino acid backbone of histone to
phosphodiester bonds of DNA
- Because octamer is positive and DNA is negatively charged, almost any DNA
sequence can be bonded to an octamer core
- DNA attachment to histones is not smooth, the core is oddly shaped and this
causes the minor groove of DNA to compress.
- Some dinucleotide in groove is easier to compress, and some nucleotides
bind more strongly.
- Each histone core also has an N terminal amino acid tail. These tails are
subject to different types of covalent modifications that control in the end the
chromatin structure and function.
- Because histones are so important, they as a result are the most highly
conserved eukaryotic proteins. Mutations in amino acid sequence in histone
proteins proves deleterious.
- Despite fact above, variant histone cores are created that differ in amino acid
sequence. With modification of amino acid tail, we get a lot of different
chromatin structures required for DNA in higher eukaryotes.
Nucleosomes have dynamic structure- and are frequently subjected to changes
catalyzed by chromatin which is an ATP dependent remodeling complex
-For DNA to be read out, multiple sites need to be accessed. DNA exposes it self by
unwinding. Thus it is available for binding.
-for chromatin, loosening of DNA- protein contacts is needed
- this is done by a atp dependent complex which remodels the chromatin. This is
done by the use of ATP to push the nucleosome resulting in the loosening of the DNA
making it available to other proteins
- these complexes work with negatively charged histone chaperone to remove all or
part of the nucleosome core from the nucleosome. This removes either H2A-H2B
histones or the whole octomeric core from the DNA.
Nucleosome are usually packed in compact chromatin fiber
chromatin usually not seen as beads on string formation but rather just layers of
the beads on a string on topic of one another.
- what causes this? Histone tails (H4) linking to each other.