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DNA Replication Complex
By Mikaela Holt, Matt Martin, and Alec Gautier
DNA Replication Complex: Overview
Common Misconceptions Regarding the Complex
The DNA replication complex is a commonly described as a “railroad track” in which DNA polymerase moves constantly along the parent DNA
strand replicating DNA all the while. That however is not case.
Firstly, in a DNA replication complex, the proteins which synthesize DNA are thought to be congregated into one single large complex as opposed
to separate enzymes which all latch onto the parent chain when needed.
Secondly, in a DNA replication complex, the complex does not move up and down the parent strand of DNA. It is thought that the DNA is actually
what moves through the complex which is stationary and anchored to the nuclear matrix.
The current model of DNA replication complex resembles less a series of of proteins moving along strands of DNA, and more a stationary set of
proteins which reel in and
Proofreading and Repairing DNA
DNA replication is due to specificity of base pairing and DNA polymerase. 1 in 105 Base Pairing errors, 1 in 1010 errors with DNA polymerase.
Mismatch Repair: Enzymes remove and replace incorrectly paired nucleotides resulting from replication errors. A defect in repair enzymes could
lead to colon cancer. About 130 repair enzymes have been found in humans.
DNA cutting enzyme nuclease cuts damaged strands of DNA so it can be recopied.
Evolutionary Significance of Altered DNA Nucleotides
Error rate within the DNA is extremely low after the proofreading and repair process, mistakes do slip through.
Once a mistake is made (replication of mismatched nucleotide pairs), it is permanent in the daughter molecules and any
subsequent molecules.
Mistakes in DNA nucleotide pairs = a mutation.
Mutations in gametes DNA of an organism are passed onto future generations
Mutations, harmful or beneficial, give way to variation among organisms allowing natural selection to occur
of new species.
appearance
Cooperation between a low mutation rate and systematic replication or and/or repair have created the immense diversity of
Earth’s organisms.
Hox Mutation in flies,
obviously a harmful
one.
Replicating the Ends of DNA Molecules
In linear DNA, replication cannot occur on the 5’ ends of daughter DNA strands. This is because DNA polymerase can only add nucleotides to the 3’
end. Because of this, DNA strands would be made unevenly with progressively shorter ends. To combat this, organisms with linear DNA (Eukaryotes),
have structures called telomeres which prevent the ends of DNA from becoming uneven.
Telomeres do not contain new genes. The telomeres actually consist of multiple repetitions of a single nucleotide .
Telomeres also do not completely prevent the eroding away of genes; the telomere merely slows the process of DNA degradation. Telomeres also
tend to be shorter in cells that have divided multiple times. In cultured cells or somatic cells of an older organism telomeres will likely be shorter.
In eukaryotic germ cells, there is an enzyme known as telomerase which lengthens the telomeres and restoring them to their original length to
compensate for the loss in DNA that occurs during replication.
A picture of
telomeres
Concept 13.3
Bacterial chromosome is double stranded, circular DNA. E. Coli has the most DNA of all bacteria with 4.6 million nucleotide pairs (~4400
genes). It is nearly 500 times length of cell when stretched out.
Bacteria do not have a membrane surrounding the nucleotide.
Eukaryotic chromosomes are linear, double helix. Humans have 1.5x108 nucleotides.
Chromatin varies how packed it is throughout the cell cycle.
Heterochromatin is visible as irregular clumps with a light microscope. Euchromatin is less condensed, more dispersed chromatin.
Exploring Chromatin Packing in a Eukaryotic Chromosome:
Levels of DNA coiling and folding
The Double Helix, Histones, and Nucleosomes
Nucleosomes
“Beads on a string”
Double Helix
Each “ribbon” represents the
sugar-phosphate backbone,
phosphates exert a
negative charge on the
outside of the ribbon
Histones
● Each small histone has 100 amino acids, but
are almost equal in mass to the DNA itselfresponsible for the first level of DNA packing
in chromatin.
● >⅕ are positively charged, bonds to
negatively charged DNA
● Four types of histone common in chromatin:
H2A, H2B, H3, and H4
● All four types are very similar among
eukaryotes, signifies the importance of
histones in DNA organization and
● “DNA wound twice around essentially a
ball of protein, composed of two
molecules each of the four main histone
types
● A histone tail, the amino end of the
histone, extends outward from the
nucleosome
Fiber, Loops, and the Metaphase Chromosome
300-nm Fiber
30-nm Fiber
Interactions between the
histone tails of one
nucleosome and the linker
DNA of another
Histone, H1, is introduced and
the 10-nm fiber coils and
folds and forms a 30 -nm
fiber
●
30-nm fiber forms
looped domains
attached to a
chromosome
scaffold composed of
proteins, to make a
300-nm fiber
Metaphase Chromosome
●
●
Looped domains coil and fold
around themselves in a way not
fully understood, compacting
into the shape of a chromosome
Complicated organization is not
known, for particular genes
always end up in the same place
on all metaphase chromosomes