Download - Role of Chromatin in Cytogenetics
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Chromosome Structure
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DefinitionA chromosome is an organized structure of DNA and protein
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Historical Background•Walter Flemming (1882)
•Theodor Boveri (1902)•Walter Stanborough Sutton (1903)•Edmund Beecher Wilson (1905)•Theophilus Shickel Painter (1923)•Joe Hin Tjio and Albert Levan
(1956)
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DNA Packaging
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DNA Organization
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ChromatinChromatin is the combination of
DNA and proteins that make up the contents of the nucleus of a cell.
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Chromatin Function•to package DNA into a smaller
volume to fit in the cell (1.2 × 1010 miles of DNA unwound)
•to strengthen the DNA to allow mitosis
•to prevent DNA damage•to control gene expression and
DNA replication
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Chromatin organization
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Chromatin Organization•DNA wraps around histone proteins forming nucleosomes; the "beads on a string" structure (euchromatin).
•Multiple histones wrap into a 30 nm fibre consisting of nucleosome arrays in their most compact form (heterochromatin).
•Higher-level DNA packaging of the 30 nm fibre into the metaphase chromosome (during mitosis and meiosis).
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Beads on a string
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Histone Modification:
• Methylation- increases packing
• Phosphorylation – decreases packing
• Acetylation – decreases packing
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Chromosome Arms
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The Long and Short of it all
The position is on the chromosome's short arm (p for petit in French); q
indicates the long arm (chosen as next letter in alphabet after p).
The bands are visible under a microscope when the chromosome
is suitably stained. Each of the bands is numbered, beginning with
1 for the band nearest the centromere. Sub-bands and sub-sub-bands are visible at higher
resolution.
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Centromere• Described by Flemming (1880’s) as a “primary constriction” of the chromosome
• The centromere is the part of a chromosome that links sister chromatids. During mitosis, spindle fibers attach to the centromere via
the kinetochore.
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The complexity
of the centromere
…
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Cohesin•Protein complex SCC1 (3p26.1)
SCC3 (3q22.3)
SMC1 (Xp11.22)
SMC3 (10q25.2)
•Regulates separation of sister chromatids
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NOR• Region around which the nucleolus forms
right after cell division• Contained within the satellites on acrocentric
chromosomes• Identified using a silver stain technique-
stains satellites dark blue
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Telomere - TTAGGGA telomere is a region of repetitive nucleotide sequences at each end of a
chromatid, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes
• Hermann Muller (1930’) – X-ray experiments to break and fuse chromosomes together; telomeres were resistant to breakage.
• 15,000 base pairs• Prevent chromosomes from fusing with each other
• Prevent chromosomes from loosing sequences at the ends• Usually lose 25-200 base pairs each division
• Cell senescence as soon as telomere reaches a critical length.
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X- inactivation•X contains over a 1000 genes whereas Y is gene poor
•Dosage effect/ dosage compensation
•One chromosome randomly inactivates and produces a dark staining
•B_ _ _ B_ _ _ (Mary Lyon, 1961)* “random X-inactivation occurs at 6.5 days of embryogenesis”- V. najfeld
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References
Lyon MF (1961) Gene action in the X-chromosome of the mouse (MusmusculusL). Nature 190: 372–373.
Diaz-Martinez, Laura Angelica; and Yu, Hongtao (December 2010) Chromosome Condensation and Cohesion. In : encyclopedia of Life Sciences (ELS). John Wiley & Sons, Ltd: Chichester. DOI:10.1002/9780470015902.A0022534
Cheeseman, I. M., & Desai, A. Molecular architecture of the kinetochore-microtubule interface. Nature Reviews Molecular Cell Biology 9, 33–46 (2008) doi:10.1038/nrm2310
Bednar, J., et al. Nucleosomes, linker DNA, and linker histones form a unique structural motif that directs the higher-order folding and compaction of chromatin. Proceedings of the National Academy of Sciences 95, 14173–14178 (1998)
Fischle, W., et al. Histone and chromatin cross-talk. Current Opinion in Cellular Biology 15, 172–183 (2003)
Ford, C. E., & Hamerton, J. L. The chromosomes of man. Nature 178, 1020–1023 (1956) doi:10.1038/1781020a0