Presentation on theme: "Molecular Basis of Inheritance Chapter 16. DNA as Genetic Material Watson and Crick – 1 st scientists to propose structure of DNA - responsible for transmission."— Presentation transcript:
Molecular Basis of Inheritance Chapter 16
DNA as Genetic Material Watson and Crick – 1 st scientists to propose structure of DNA - responsible for transmission of traits from 1 generation to next. Requires precise transmission occurs.
Griffith - injected live bacterial strains into mice. Mixed R strain of bacteria (harmless) with heat-killed S strain (harmful) and injected it. After mouse died, removed strain from mouse.
Transformation - change in genotype and phenotype due to assimilation of foreign substance (now DNA) by cell.
Substance found to be DNA - supported by injecting bacteria into viruses. Viruses consist of DNA (sometimes RNA) enclosed by protective coat of protein.
To replicate - virus infects host cell; takes over cell’s metabolic machinery. Viruses that specifically attack bacteria - bacteriophages (phages) Hershey and Chase labeled protein and DNA - injected them into bacteria.
Hershey and Chase concluded that injected DNA of phage provides genetic information that makes infected cells produce new viral DNA and proteins, which assemble into new viruses. DNA doubles prior to mitosis.
By 1940’s - discovered that DNA was made of bases. Adenine, thymine, cytosine, and guanine. Chargaff’s rules - an even amount of thymine and adenine. (and guanine and cytosine)
Was known that sugar of one nucleotide attached to phosphate of another - forms backbone of DNA.
Watson 1 st to figure out that DNA was in helix shape + specific distance between nucleotides. Partnered with Crick – came up with double stranded model of DNA - double helix.
Found that purine has to pair with pyrimidine to achieve distance needed. Knew that adenine always paired with thymine and cytosine always with guanine.
Discovered that bases were held together by hydrogen bonds. Adenine forms 2 hydrogen bonds only with thymine; guanine forms 3 hydrogen bonds only with cytosine.
Each gene found to have unique sequence of nitrogen bases - DNA strands not all the same.
DNA Replication and Repair Watson and Crick discovered each strand of DNA can make template to make more DNA. Cell copies DNA - each strand forms as template to determine new complementary bases. Nucleotides pair in complementary fashion, one by one.
Happens by semiconservative replication - each DNA molecule has one parent strand and one daughter strand. Idea later supported through bacteria studies.
Even though process is amazingly quick, only about 1 in a billion nucleotides copied wrong. Proteins and enzymes also part of process, not just nucleotides.
Origins of replication - where replication process begins. Bacteria - 1 site - replication looks like bubble moving along DNA. Eukaryotes - many origins of replication on each chromosome. Origin sites - DNA strands separate forming replication “bubble” with replication forks at each end.
Elongation of DNA catalyzed by DNA polymerase. Polymerase adds complementary bases to growing strand of new DNA.
Strands of DNA - antiparallel. Sugar-phosphate backbones run in opposite directions. Each end of strand labeled either 5’ end or 3’ end.
Nucleotides only be added to 3’ end. DNA strand can only elongate from 5’ end to 3’ end. Replication fork - problem - system because strands run in opposite directions (antiparallel)
1 parent strand (leading strand - one that runs 3’ to 5’) used as template to keep complementary strand continuous. Other strand (lagging strand - one that runs 5’ to 3’) copied from fork in small segments - Okazaki fragments.
Fragments “glued” together by DNA ligase to form backbone (made of sugar and phosphate) of single DNA strand.
Polymerase adds nucleotides to strands, cannot start whole process. Done by a piece of RNA - primer. Primase links ribonucleotides that are complementary to DNA template into primer.
Once primer formed, polymerase can add DNA nucleotides to growing daughter strand of DNA. Later - different DNA polymerase replaces original RNA with new complementary DNA nucleotides - there is no RNA left in strand.
Helicase - untwists double helix of DNA at replication fork. Single-strand binding proteins help keep strands apart from one another during replication.
At replication fork, leading strand copied continuously into fork from single primer. Lagging strand copied away from fork in short segments, each requiring new primer.
Original errors in reading of template occur. Enzyme (DNA polymerase) removes mistake and replaces it. Some things can alter DNA outside of body.
X-rays and UV rays can alter DNA after replication. Mistakes can be fixed after DNA synthesis because cell continually monitors DNA. Mismatch repair, special enzymes fix incorrectly paired nucleotides - happens in certain types of cancers.
Nucleotide excision repair, nuclease cuts out segment of damaged strand.
Xeroderma pigmentosa (genetic disease) cannot go through process. Disease prevents person from going in sun because UV rays interfere with DNA replication. More susceptible to skin cancer because they cannot fix mistakes.
Limitations in DNA polymerase create problems for linear DNA of eukaryotic chromosomes. Ends of DNA strand can break down from constant replication.
Ends of eukaryotic chromosomal DNA molecules – telomeres - special nucleotide sequences. Telomeres protect genes from being eroded through multiple rounds of DNA replication.
When telomeres shorten, telomerase uses piece of RNA to lengthen telomere.
Telomerase not present in all cells - life span to certain tissues or organism itself. Important for telomerase to be present in gamete cells so they can pass long telomeres on to zygote. Active telomerase in body cells can be responsible for cancer cells because cells keep dividing.