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MCB 121 Lecture 19

MCB 121 Lecture 19 - MCB 121(Last Lecture Genome...

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MCB 121 (Last Lecture) Genome Instability + Cancer I. DNA damage/mutation II. Genetic mechanism of cancer III. Double-strand break repair IV. Genome Instability -------------------------------------------------------------- Intrinsic Cause of DNA Damage: - free radicals created by the metabolisms in the cell cause oxidative damage to DNA - Misincorporation of nucleotides by DNA polymerase = occurs at high frequency ~ 10^-7 - Replication slippage = as the DAN polymerase replicating the DNA, there is slippage which causes the shifting of polymerase relative to the template strand. = results the expansion of repeated elements - Errors in chromosome segregation = occur either in mitosis or meiosis = in mitosis, it can be chromosome lost or wrong number of chromosomes (result anuiploidy ) = anuiploidy: the cells that have wrong number of chromosomes ex. trisomy in 21 = Down syndrome - unequal crossing over = repeated elements can undergo recombination with each other in the genome = unequal crossing over can result deletion/insertion of chromosomal region Extrinsic Causes of DNA Damage: - γ-ray, X-ray, and UV light = ionizing radiation = gamma-ray and X-ray causes double strand breaks = not the high energy of the rays breaking DNA. = gamma-ray and X-ray create oxidative damage by creating free radicals near the nucleotide backbone which causes double strand break. = UV light causes thymine dimers (two adjacent thymines are cross-linked together) = causes the block of DNA replication if thymine dimers aren't repaired - exposure of DNA crosslinking agent = forms crosslink between the Watson & Crick strands of DNA = block the polymerases from moving through the area of crosslinked region of DNA ex. Cis-platin (drug used to treat particular cancer) - exposure of DNA alkyating agent = that's normally used to modify bases = this can cause single nucleotide changes or mutation II. Genetic Mechanism of Cancer
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Cancers are genetic disease. Steps of cancer: 1. loss of growth control 2. loss of checkpoint functions (ability to detect the DNA damage) 3. growth of genome instability 4. activation of telomerase (leads to immortal cell) 1) Loss of growth control: Cells are controlled by 1) genes that control cell cycle, 2) hormone signaling, and 3) signal transduction Single mutation can occur to allow these type of events to go out of control.
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