Genes & Chromosomes
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Transcript of Genes & Chromosomes
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Genes & Chromosomes
Part III, Chapters 24, 25
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Central Dogma • DNA replicates more DNA for
daughters• (Gene w/in) DNA transcribed
RNA– Gene = segment of DNA– Encodes info to produce funct’l biol
product• RNA translated protein
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Genome• Sum of all DNA
– Genes + noncoding regions• Chromosomes
– Each w/ single, duplex DNA helix– Contain many genes
•Historical: One gene = one enzyme•Now: One gene = one polypeptide•Some genes code for tRNAs, rRNAs•Some DNA sequences (“genes”) =
recognition sites for beginning/ending repl’n, transcr’n
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• Most gene products are “proteins”– Made of aa’s in partic sequence– Each aa encoded in DNA as 3
nucleotide seq along 1 strand of dbl helix
– How many nucleotides (or bp’s) needed for prot of 350 aa’s?
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Prokaryotic DNA• Viruses
– Rel small amt DNA•5K to 170K base pairs (bp’s)
– One chromosome•Chromosome = “packaged” DNA
– Many circular
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• Bacterial DNA -- larger than viral– E. coli ~4.6 x 106 bp’s– Both chromosomal, extrachromosomal
• Usually 1 chromosome/cell• Extrachromosomal = plasmid
– 103-105 bp’s– Replicate– Impt to antibiotic resistance
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Chromosomes Complex
Packaging reduces E.coli DNA 850x
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Eukaryotic DNA
• Many chromosomes– Single
human cell DNA ~ 2 m
• Must be efficiently packaged
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Euk Chromosomes
• Prok’s – usually only 1 cy of each gene (but exceptions)
• Euk’s (ex: human)– Book: coding region (genes coding
for prot’s) ~ 1.5% total human genome•Exons
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• Euk’s (ex: mouse): ~30% repetitive– “Junk”?– Non-transcribed seq’s
•Centromeres – impt during cell division •Telomeres – help stabilize DNA• Introns – “intervening” seq’s
– Function unclear
– May be longer than coding seq’s (= exons)
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Supercoiling• DNA helix is coil
– Relaxed coil not bent– BUT can coil upon itself supercoil
• Due to packing; constraints; tension• Superhelical turn = crossover• Impt to repl’n, transcr’n
– Helix must relax so can open, expose bp’s
– Must unwind from supercoiling
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Topoisomerases
• Enz’s in bacteria, euk’s• Cleave phosphodiester bonds in 1/both
strands– Where are these impt in nucleic acids?– Type I – cleaves 1 strand– Type II – cleaves both strands
• After cleavage, rewind DNA + reform phosphodiester bond(s)
• Result – supercoil removed
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Type I
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Type II
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DNA Packaging
• Chromosomes = packaged DNA– Common euk “X”- “Y”-looking
structures– Each = single, uninterrupted mol DNA
• Chromatin = chromosomal material – Equiv amts DNA + protein– Some RNA also assoc’d
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1st Level Pakaging in Euk’s
Around Histones
• DNA bound tightly to histones
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• Basic prot’s• About 50% chromosomal mat’l• 5 types
– All w/ many +-charged aa’s – Differ in size, amt +/- charged aa’s
•What aa’s are + charged?•Why might + charged prot be assoc’d w/
DNA helix?• 1o structures well conserved
across species
Histones
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• Must remove 1 helical turn in DNA to wind around histone – Topoisomeras
es impt
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• Histones bind @ specific locations on DNA – Mostly AT-
rich areas
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Nucleosome • Histone wrapped w/ DNA
7x compaction of DNA• Core = 8 histones (2 copies of 4 diff
histone prot’s)• ~140 bp DNA wraps around core• Linker region -- ~ 60 bp’s extend to
next nucleosome• Another histone prot may“sit” outside
– Stabilizes
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Chromatin• Further-
structured chromosomal mat’l
• Repeating units of nucleosomes
• “Beads on a string”– Flexibly
jointed chain
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30 nm Fiber• Further nucleosome packing • ~100x compaction• Some nucleosomes not inc’d into
tight structure
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Rosettes• Fiber loops around nuclear scaffold
– Proteins + topoisomerases incorporated• 20-100K bp’s per loop
– Related genes in loop•Book ex: Drosophila loop w/ complete set
genes coding for histones• ~6 loops per rosette = ~ 450K bp’s/
rosette• Further coiling, compaction
10,000X compaction total
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Semiconservative Replication
• 2 DNA strands/helix• Nucleotide seq of 1 strand
automatically specifies complementary strand seq – Base pairing rule: A w/ T and G w/ C
ONLY in healthy helix– Each strand serves as template for
partner• “Semiconservative”
– Semi – partly– Conserved parent strand
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• DNA repl’n daughter cell w/ own helix– 1 strand is
parental (served as template)
– 2nd strand is newly synth’d
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Definitions• Template
– DNA strand w/ precise info for synth complementary strand
– = parental strand during repl’n• Origin
– Unique point on DNA helix (strand) @ which repl’n begins
• Replication Fork– Site of unwinding of parental strand and
synth of daughter strand• NOTE: helix unwinding crucial to repl’n success
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• Repl’n Fork – cont’d– Bidirectional
repl’n • 2 repl’n forks
simultaneously synth daughter strands
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At Replication Fork
• Both parental strands serve as templates– Simultaneous synth of daughter cell dbl
helices• Expected
– Helix unwinds repl’n fork– Get 2 free ends
•1 end 5’ –PO4, 1 end 3’ –PO4
•REMEMBER: paired strands of helix antiparallel
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• Expected -- cont’d– Repl’n each strand at end of parent
•One strand will replicate 5’ 3’– Direction of active repl’n 5’ 3’
– Happens @ parent strand w/ 3’ end
– Yields 2nd antiparallel dbl helix
•One strand will replicate 3’ 5’– Direction of active repl’n 3’ 5’
– Happens @ parent strand w/ 5’ end
– Yields antiparallel dbl helix
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• But, exper’l evidence:– Repl’n ALWAYS 5’ 3’
•Can envision at parental strand w/ 3’ end
•What happens at other parental strand??
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Okazaki Fragments
• Discovered by Dr. Okazaki– Found near repl’n fork
• Small segments daughter strand DNA synth’d 5’ 3’ – Along parental template strand w/ 5’
end• Get series small DNA
segments/fragments– So synth along this strand in opp
direction of overall replication (or of unwinding of repl’n fork)
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• “Lagging strand”– Takes longer to synth fragments + join
them• Other parental strand, w/ continuous
synth “leading strand”• W/ repl’n, fragments joined
enzymatically complete daughter strand
• Overall, repl’n on both strands in 5’ 3’ direction (w/ respect to daughter)
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• Don’t be confused w/ bi-directional repl’n– Bidirectional: >1 repl’n fork initiating
repl’n simultaneously– At each fork, repl’n takes place along
both strands– At each fork, repl’n in 5’ 3’ direction
ONLY along each strand
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Enz’s That Degrade DNA• Exonucleases – degrade DNA
from one end of molecule– Some digest one strand 3’ 5’– Some digest in 5’ 3’ direction
• Endonucleases – degrade DNA from any site