04 Mitosis and Meiosis (1)

04 Mitosis and Meiosis (1) - Scientists recently discovered...

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Condition causes premature aging and death in teens. Scientists recently discovered the secret of Hutchinson-Gilford Progeria
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Hutchinson-Gilford Progeria Hutchinson-Gilford Progeria is an extremely rare genetic disease that accelerates the process of aging 10-fold. About 40 cases are known worldwide Children have the body of a 70 year old. Symptoms are baldness, wrinkled skin, heart disease. Mental development is normal. Children die in their teens of olds age Recently, it was discovered that the disease is caused by a mutation in the lamin A gene. Lamin A protein is involved in attachment of DNA to the nuclear envelope A point mutation caused bad splicing and led to loss of part of the Lamin A gene. Nuclei were misshapen and chromatin was damaged. The condition would be inherited in a dominant fashion (haplo insufficient) Why do you think this condition is so rare?
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DNA replication and cell division are amazing processes. Each nucleus is about 5 microns wide (10x thinner than a human hair) and has over 2 meters of DNA that must be replicated perfectly and equally divided between two identical cells Cell DNA replicates within 2-3 hours with very few mistakes The process of mitosis forms two identical cells DNA replication and cell division
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Occurs in the S phase of cell cycle Semiconservative replication: each DNA strand is a template for synthesis of the complementary strand Origin of replication: DNA synthesis starts at these structures Replication forks: where the DNA is unwound and new nucleotides are added. There are two diverging replication forks (bidirectional) Enzyme complex: each replication fork contains DNA polymerase, primase to make primers, helicase to unwind DNA, ligase to join DNA, and topoisomerase to relieve tension Where is the other replication fork? DNA replication
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Polymerization of DNA DNA polymerase: adds nucleotides to the 3’ end of each strand. Single strands are anti parallel and synthesis must proceed in different directions on each strand Polymerization requires the following: dATP, dGTP, dCTP, dTTP (collectively the dNTPs) single-stranded template RNA primer with free 3’ OH to accept the incoming nucleotide 2 DNA polymerases (one on each strand)
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Polymerization of DNA What proteins are required for DNA synthesis? Primase: makes a short RNA primer to initiate DNA synthesis Helicase: unwinds DNA helix at the replication fork Topoisomerase: cuts DNA upstream of the fork to relax supercoils formed by unwinding DNA binding proteins: prevent single strands from joining again DNA ligase: joins short Okazaki fragments to the lagging strand
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DNA synthesis can only work from 5’ to 3’ direction, since strands are anti parallel, DNA synthesis differs on the two strands leading strand: DNA replication occurs continuously on this strand lagging strand: DNA replication must be discontinuous here Okazaki fragments: short fragments of DNA are made 5’ to 3’ as the replication fork unwinds 5’ 3’ Leading and lagging strands Error in text on page 97, fig 4-6
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Synthesis of the lagging strand
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This note was uploaded on 04/23/2008 for the course BY 214 taught by Professor Woodworth during the Spring '07 term at Clarkson University .

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04 Mitosis and Meiosis (1) - Scientists recently discovered...

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