The structure of part of a DNA double helix

Transcription

1 The structure of part of a DNA double helix

2 Human chromosomes (grey) capped by telomeres (white).

3 The chromosomes contain our genome in their DNA molecules. As early as the 1930s, Hermann Muller (Nobel Prize 1946) and Barbara McClintock (Nobel Prize 1983) had observed that the structures at the ends of the chromosomes, the so-called telomeres, seemed to prevent the chromosomes from attaching to each other. They suspected that the telomeres could have a protective role, but how they operate remained an enigma.

4 When studying the chromosomes of Tetrahymena, Elizabeth Blackburn identified a DNA sequence that was repeated several times at the ends of the chromosomes. The function of this sequence, CCCCAA, was unclear. tetrahymena

5 A type of Yeast At the same time, Jack Szostak had made the observation that a linear DNA molecule, a type of minichromosome, is rapidly degraded when introduced into yeast cells.

6 Blackburn presented her results at a conference in They caught Jack Szostak's interest and he and Blackburn decided to perform an experiment that would cross the boundaries between very distant species. The results, which were published in 198, were striking the telomere DNA sequence protected the minichromosomes from degradation. As telomere DNA from one organism, Tetrahymena, protected chromosomes in an entirely different one, yeast, this demonstrated the existence of a previously unrecognized fundamental mechanism.

7 An enzyme that builds telomeres. Carol Greider, then a graduate student, and her supervisor Blackburn started to investigate if the formation of telomere DNA could be due to an unknown enzyme. On Christmas Day, 1984, Greider discovered signs of enzymatic activity in a cell extract. Greider and Blackburn named the enzyme telomerase,

8

9 Telomeres delay ageing of the cell An important piece in the puzzle human ageing, cancer, and stem cells

10 1 Let θ T = arccos. 3 Suppose q θt = π pθt = p qπ. In light of it, we have cos( θ ) = cos( qπ ) = ± 1. p T 1 7 cosθ =, cos(θ T T ) = 3 3,... c Claim cos( p θ ) =. T 3 p cos( A + B) = cos Acos B sin Asin B. Don t like it.

11 cos( n + 1) Γ = cosnγcosγ sin nγsin Γ. cos( n 1) Γ = cosnγcos Γ + sin nγsin Γ. cos( n + 1) Γ + cos( n 1) Γ = cosnγcos Γ cos( n + 1) Γ = cosnγcos Γ cos( n 1) Γ cos( n That is, c + 1) Γ = = c 3 c c 3 n c 1 n+ 1 = n which is not divisible by 3. n n+ 1 n c 3 3, 3 n+ 1 n 1 n 1 c n 1.

12 (6) ) ) ) ) ) ((((((6) (6) (6) = = + = mod 10 (6) 133 mod 43 (85) 133 mod 85 (9) 133 mod 9 (99) 133 mod 99 (36) 133 mod 36 (10)

13 43* * *6 6 mod 133.

14

15 Beriberi - Symptoms include irritability and fatigue, and later, numbness in the fingers and toes, seizures and decreased mental ability. Dutch physician Eijkman, under the influence of Pasteur, believed a bacterium caused beriberi, but failed to identify the agent. (The pre-critical part.) He associated the human disease to similar symptoms observed in hens. (What symptoms?)

16 It is showed that the hens developed the beriberi-like disease soon after their feed was changed to polished rice... and by adding rice bran (the parts removed in polishing) to the hens' food, the disease could be cured.

17 Eijkman and his successor, later used water or ethanol to extract the mysterious antineuritic factor from rice hulls. "There is present in rice polishings a substance different from protein and salts," the two researchers wrote in 1906, "which is indispensable to health and the lack of which causes nutritional polyneuritis." (This work earned him the Nobel prize in 199.) In 196 B. C. P. Jansen and W. Donath, two Dutch chemists working in Eijkman's old laboratory in Jakarta, crystallized the water-soluble antineuritic factor--now called vitamin B1, from rice bran. (Bacterium conjecture really being refuted?)

18 Salt Sodium Chloride Sugar Carbohydrates Protein Amines It is now known that various vitamins contain no amines at all. An example? So the name Vitamin serves as a hallmark of human error and sign of critical thinking. Closing in on Rickets.

19 Sporadic reports of cures for rickets surfaced, including one by feeding cod-liver oil. McCollum in US found out that fat-soluble vitamin A can cure night blindness. It is known that cod-liver oil is rich in vitamin A. This leads to the conjecture that vitamin A was a cure for rickets.

20 McCollum began by heating and aerating the oil to destroy its vitamin A. As expected, the treated oil no longer cured night blindness.. But, to everyone's surprise, it did remain effective against rickets. Clearly, an unknown essential nutrient was responsible. He dubbed the new miracle worker Vitamin D. In recognition of his seminal research on vitamins, McCollum was elected a member of the National Academy of Sciences (USA). (Election to the Academy is considered one of the highest honors that can be accorded a scientist or engineer. The Academy membership is comprised of approximately,000 members and 300 foreign associates, of whom more than 180 have won Nobel Prizes.).

21 Early in the 0 th century, Windaus had embarked on his study of cholesterol and related sterols, about which virtually nothing was known at the time. From the very start, he believed that investigations into the structure of these molecules would yield unexpected results. (198 Nobel Prize in Chemistry) Sterols are nitrogen-free secondary alcohols of high molecular weight

22 In 197, Windaus et al. deduce that ergosterol is the likely parent substance of vitamin D in food. In 1936, Windaus deduces the structure of vitamin D3 produced in skin, and identifies the structure of Its parent molecule, 7-dehydrocholesterol. In 1968, it is shown that an active Vitamin D metabolite is produced in the liver. A final active form of vitamin D is later found to be produce in kidneys. (Hormone?) By 1975, it is confirmed that vitamin D helps to increase the absorption of Ca In the intestine.

23 1,5-dihydroxyvitamin D_3 -- a hormone that not only controls calcium metabolism by increasing intestinal calcium absorption and bone calcium mobilization, but also has many other effects e.g cancer control, immune system. (Eat well and exercise!)