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attention is now turning to the possible clinical application of this knowledge: If telomerase can be deactivated in tumor cells, the cells may stop dividing or die, thereby eliminating the cancer. Further, studying normal telomere shortening, which appears to act as a biological clock, may help us understand the aging process and senescence. R. Britten and his colleagues, using the technique of DNA-DNA hybridization, rst systematically analyzed the repetitiveness of the DNA within eukaryotes. When DNA is heated, it denatures or unwinds into single strands; when it cools, it renatures. The rate of renaturation depends on the DNA sequences. If the sample contains DNA with repeated sequences, it will hybridize
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Tamarin: Principles of Genetics, Seventh Edition
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III. Molecular Genetics
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15. The Eukaryotic Chromosome
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The Eukaryotic Chromosome
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The t-loop at the end of the mammalian telomere. (a) A diagram of how the t-loop is formed by the interdigitation of the 3 end of the telomere into the double helix. (b) Electron micrograph of a t-loop from a mouse liver cell. The loop is about 10,000 bases around. ([b] From Jack D.
Grif th, et al., Mammalian telomeres end in a large duplex loop in Cell, 97:503 14, May 14, 1999. Copyright Cell Press.)
faster than DNA that does not have repeated sequences. From these studies, Britten and his colleagues found that eukaryotic chromosomes contain regions of unique, moderately repetitive, and highly repetitive DNA. Unique DNA is, as its name implies, DNA with unrepeated sequences. Repetitive DNA is DNA whose sequences are repeated in the genome. Satellite DNA, found around centromeres (see g. 15.20), is highly repetitive DNA with a unique repeat length of about two hundred base pairs. Given the
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Roy J. Britten (1919 ).
(Courtesy of Dr. Roy J. Britten.)
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quantity of satellite DNA per cell, there must be more than one million repetitions of this two-hundrednucleotide sequence in higher eukaryotes. At the other end of the spectrum is unique DNA, which makes up most of the transcribed genes of an organism. The rest of the DNA is repetitive DNA in a few to several hundred thousand copies. This repetitive DNA comprises at least three categories. One is junk DNA, DNA that is not useful to the organism, made up of untranscribed and parasitic sequences (selfish DNA). Another category is transcribed genes in many copies that have diverged from each other, such as antibody, collagen, and globin genes. We use the term gene family to refer to genes that have arisen by duplication, with or without divergence, from an ancestral gene. And finally, transcribed genes in many copies that are virtually identical, such as ribosomal RNA and histone genes, make up a third category of repetitive DNA.
Junk DNA
We saw in chapter 13 that transposons in prokaryotes are generally viewed as sel sh or parasitic: They serve no purpose to the cell. The transposons replicate on their own, increasing in number. Eukaryotic transposons are mostly retrotransposons, transposable elements that move by way of an RNA intermediate. That is, the retrotransposon is transcribed into RNA and then, by reverse transcription, converted to a cDNA that is then inserted into the genome.These elements can make up 50% of the eukaryotic genome, existing in hundreds of thousands of copies. They generally fall into two categories: LINES and SINES. Long interspersed elements (LINES), are up to seven thousand base pairs each and contain genes for reverse transcription, RNA binding, and endonuclease activity. They thus have the ability to jump by way of an RNA intermediate. Human DNA is believed to be composed of about 15% LINES. Short interspersed elements (SINES) are generally derivatives of transfer RNA genes and do not have the ability to retrotranspose on their own.That is, in the past, their transcripts were modi ed, converted to cDNA by reverse transcription, and then reinserted into the host s
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