Telomere Structure

Telomeres are the natural ends of a chromosome (see Figure 2.6). Pioneering work by Hermann Muller (on fruit flies) and Barbara McClintock (on corn) showed that chromosome breaks produce unstable ends that have a tendency to stick together and enable the chromosome to be degraded. Because attachment and degradation don’t happen to the ends of a chromosome that has telomeres, the telomeres must serve as caps that stabilize the chromosome. Telomeres also provide a means of replicating the ends of the chromosome, as we will see in Chapter 9.

Telomeres have now been isolated from protozoans, plants, humans, and other organisms; most are similar in structure. These telomeric sequences are usually repeated units of a series of adenine or thymine nucleotides followed by several guanine nucleotides, taking the form 5′—(A or T)mGn—3′, where m ranges from 1 to 4 and n is 2 or more. For example, the repeating unit in human telomeres is 5′—TTAGGG—3′, which may be repeated from hundreds to thousands of times. The sequence is always oriented with the string of Gs and Cs toward the end of the chromosome, as shown here:

image

The G-rich strand often protrudes beyond the complementary C-rich strand at the end of the chromosome (­Figure 8.21a), in which case it is called the 3′ overhang. The 3′ overhang in mammalian telomeres is from 50 to 500 nucleotides long. Special proteins bind to the G-rich single-stranded sequence, protecting the telomere from degradation and preventing the ends of chromosomes from sticking together. A multiprotein complex called shelterin binds to telomeres and protects the ends of the DNA from being inadvertently repaired as a double-strand break in the DNA. In some cells, the 3′ overhang may fold over and pair with a short stretch of DNA to form a structure called the t-loop, which also functions in protecting the end of the telomere from degradation (Figure 8.21b).

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Figure 8.21: DNA at the ends of eukaryotic chromosomes consists of telomeric sequences. (a) The G-rich strand at the telomere is longer than the C-rich strand. (b) In some cells, the G-rich strand folds over and pairs with a short stretch of DNA to form a t-loop.

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CONCEPTS

A telomere is the stabilizing end of a chromosome. At the end of each telomere are many short telomeric sequences.

image CONCEPT CHECK 10

Which of the following is a characteristic of DNA sequences at the telomeres?

  1. One strand consists of guanine and adenine or thymine nucleotides.

  2. They consist of repeated sequences.

  3. One strand protrudes beyond the other, creating some single-stranded DNA at the end.

  4. All of the above

d