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Regulation of Gene Expression – Part III Spring 2013 - Althoff Reference: Mader & Windelspecht Ch. 13) • Lec 20 Gene Mutations • • • • • Gene Mutations A gene mutations is __________ change in the _____________________ in DNA The “change” can result in a) no effect on protein activity to b) complete inactivity A ____________________ is one that occurs in _______________ and can be passed to subsequent generations. A ____________________ is one that occurs in ___________—and therefore may only affect a small number of cells in a tissue Somatic mutations _________ passed on to future generations Causes – 2 basic types • ________________ mutations = happen for no apparent reason…a result of abnormalities in normal biological processes • ___________ mutations = induced by ____________ ______________. They may result from exposure to a) toxic chemicals b) radiation c) other? These “exposures” “induce/cause” changes in base sequences of DNA Spontaneous Mutations • Again, associated with “normal” biological processes • Example: moveable piece of DNA, termed a ___________, may “jump” from location to another, disrupting one or more genes…leading to an abnormal product Interrupted DNA sequence Spontaneous Mutations…con’t • Again, associated with “normal” biological processes • Example: On rare occasions, a base in DNA can undergo a _________________ that leads to a mispairing during replication…a subsequent base pair change may be carried forth in future generations • This ↑example is a rare occurrence because…. _______________—the enzyme that carries out replication—__________ the new strand against the old strand and ________ mismatched nucleotides…and _______ it with the correct one • Estimates: only ___ mistake in every ___________ nucleotide pair replications Induced Mutations • Are known as _____________ • Those mutagens known to cause cancer are also known as _______________ • Sources for chemical mutagens include: a) food we eat i) AF-2 once used in Japan – now banned ii) Safrole flavoring agent once used in root beer – now banned iii) Acrylamide—a natural product found in French fries—suspected mutage b) industrial chemicals & tobacco smoke i) tobacco changes several known organic chemicals known as carcinogens Induced Mutations…con’t • Forms of radiation known to cause mutations: X-rays gamma rays Ultraviolet (UV) radiation • UV - absorbed by pyrimidines in DNA • UV - if 2 thymine molecules next to one another, UV radiation may cause them to bind together…forming _______________. Result: kink in the DNA. They can sometimes be repaired/removed by ____________ enzymes Mutations effect on Protein Activity • ____________________– change in a ________ DNA nucleotide, and, therefore, possible change in a specific amino acid ex. What results in the cell sickled red blood cell • ____________________– occur most often when 1 or more nucleotides are either a) inserted or b) deleted from DNA. Result: a completely new sequence of codons and nonfunctional protein. Ex. THE CAT ATE THE RAT. If “C” is deleted, the framework shifts resulting in… THC ATA TET HER AT Mutations Can Cause Cancer • Current estimate: ________ people will develop cancer at some time in their lives --of the affected: 1/3 of the women will die 1/4 of the males will die • 3 deadliest forms of cancer: a) lung b) colon and rectal c) breast • Cancer results from a series of accumulated mutations as noted earlier this semester (see Lab 9 & text Chapter 9) Cancer…con’t 1• __________________ genes ordinarily act as brakes on cell division…especially if abnormalities detected. 2• _______________ stimulate cell division but are turned off in fully differentiated , non-dividing cells. 3• When proto-oncogenes mutate, they become _______________ that are ______________________. 4• The result of 2 and 3: cell division occurs _____________ because a ______________ pathway that reaches from the plasma membrane to the nucleus is non-functional. Cell Signaling Pathway that Stimulates a _______________ TUMOR SUPPRESSOR GENE Cell Signaling Pathway that Stimulates an _______________________ Cancer…con’t • Recall ____________________from last lecture (#19)… • One of the 5 ways to control gene expression • Transcription factors are fundamental to a) DNA replication & repair b) cell growth & division c) __________________ d) __________________