DNA: The Blueprint of Life History Structure & Replication

History Mendel’s paper was published 1866 By the 1900’s scientists were aware that proteins and DNA were found in the nucleus –DNA discovered by Freidrich Meischer (1869); named it nuclein However, the structure of DNA was not known and proteins were thought to be the hereditary material

Fredrick Griffith (1928) –Transformation experiment with bacterial strains and mice

Oswald Avery, Maclyn McCarty, and Colin McLeod (1944) –Concluded DNA was transforming agent Alfred Hershey and Martha Chase (1952) –Supported DNA as genetic material with bacteriophage experiment

Erwin Chargaff (1950’s) –Chargaff’s Rule: A = T and C = G Rosalind Franklin and Maurice Wilkins (1950’s) –used X-ray diffraction to learn about DNA structure

James Watson and Francis Crick (1953) –Built the first 3-D model of DNA structure –Awarded Nobel Prize along with Wilkins

DNA Structure Polymer made up of nucleotides 3 basic nucleotide components –5-carbon sugar deoxyribose –Phosphate group –Nitrogen base Adenine Thymine Cytosine Guanine

Think of DNA like a twisted ladder… –The sides consist of sugar and phosphate groups bonded together –The rungs or steps consist of base pairs held together by hydrogen bonds –Strands are antiparallel – go in opposite directions

Nitrogen Bases Purines – double rings –Include adenine (A) and guanine (G) Pyrimidines – single ring –Include thymine (T) and cytosine (C) Base Pairs –A always pairs with T; 2 hydrogen bonds –C always pairs with G; 3 hydrogen bonds The order of these base pairs is what codes for making proteins

DNA and Chromosomes Remember, genes are segments of DNA and are found on chromosomes Most of the time DNA is found as chromatin, which is DNA tightly coiled around proteins called histones (together called a nucleosome) This condenses further to see visible chromosome structure

DNA Replication DNA makes copies of itself so that cells can divide –Important for growth and reproduction –Occurs in the S phase of interphase Considered semi-conservative: when a new copy is made, half of the old strand stays with a new strand –Helps reduce copy errors –Suggested by Watson and Crick

Semi-conservative

Overview of Replication DNA molecule separates into two strands Each strand serves as a template for a new strand Two new complementary strands are formed following the rules of base pairing –Rapid and accurate; only about 1 in a billion are incorrectly paired

Replication Requires ATP (energy) and the help of many enzymes –DNA Helicase: uncoils and “unzips” DNA strands by breaking hydrogen bonds between bases –DNA Polymerase: adds new nucleotides to the original srand; also proofreads for errors –DNA Ligase: helps join Okazaki fragments on the lagging strand –Nucleases – remove incorrect bases –Primase – adds RNA primers to start new strands –Topoisomerases – play a role in the “growing fork” movement and untangling and separation of chromosomes once replicated

Steps of Replication Begins at special sites called origins of replication –Two strands open and separate making a replication fork –Creates replication bubble and proceeds in both directions until entire molecule is copied

DNA polymerase moves along the strands, adding complementary bases and proofreading as it goes. Always builds from 5’ end to 3’ end (on new strand) –This has to do with the carbons in deoxyribose –The two strands run opposite directions of each other

On one side, the leading strand, DNA polymerase moves along continuously adding bases –Built toward replication fork in one long strand On the other side, the lagging strand, DNA polymerase adds the bases in groups, creating Okazaki fragments –Built moving away from the replication fork and is made in sections This is due to following the 5’ to 3’ rule.

Primers DNA Polymerase cannot initiate the synthesis of the new strand –It can only add nucleotides to an existing chain –It requires an RNA primer, a short stretch of RNA that is added to get it started –Primase enzyme joins the RNA nucleotides –The leading strand requires one primer; the lagging strand requires one for each fragment –Primers are converted back to DNA before fragments are joined together

Repair If polymerase makes an error or an error occurs after the fact, cells will use special enzymes to fix the problem – called mismatch repair –130 repair enzymes have been identified in humans Nucleotide excision repair – nucleases cuts out a damaged portion of DNA –polymerase and ligase come in and fill in the gap

Telomeres Eukaryotic chromosomes have special nucleotide sequences called telomeres at their ends –Do not contain genes –Are multiple repetitions of a short nucleotide sequence; usually TTAGGG May be 100 – 1,000 –Avoids deleting the ends due to the 5’ to 3’ rule –Enzyme telomerase restores shortened telomeres May be a link between telomerase and cancer

If this continued, the DNA would get shorter and shorter and eventually genes could be omitted.

Once the complementary base pairs are added and the strand is complete, you now have two new strands of DNA. Remember, each pairs with an original strand Helicase recoils the two to make two identical DNA molecules

29 DNA by the Numbers Each cell has about 2 m of DNA. The average human has 75 trillion cells. The average human has enough DNA to go from the earth to the sun more than 400 times. –The earth is 150 billion m or 93 million miles from the sun. DNA has a diameter of only m.