15BIS101F2013MutatLect15

Bis101001spring2013genesandgeneexpressionrlrodriguez

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Unformatted text preview: cellular function or the source serious disease. BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez ©2013 BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez 4 In this lecture: Mutations and cancer. Mutations Cancer is caused by multiple DNA mutations that allow cells to proliferate uncontrollably. Molecular Basis of Mutation. Single base pair substitutions, insertions, or Single deletions can change the way the triple code of the correct open reading frame (zero reading frame) is read. These forward mutations can lead to loss of function or a forward gene or create a new function. Suppressor Mutations. Mutations can be reversed by a back mutation or by a Mutations suppressor. A suppressor is a second mutation within the gene (intragenic) or in another gene (extragenic) another Spontaneous Mutations. These mutations are rare and occur as a result of errors These in DNA replication, tautomeric shifts in certain bases, and permanent chemical changes in nucleotides. Mutations can be caused by slippage in DNA replication. slippage Induced Mutations. Mutations can be caused or induced by chemicals or physical Mutations agents such as ionizing radiation (e.g, X-rays and ultraviolet light). These mutagens mutagens can be used to increase the rate of mutations by several orders of magnitude. can Ames Test. Bacterial assays that allows us to quickly screen thousands of Bacterial chemicals for their potential genotoxicity and carcinogenicity. The basis for this test genotoxicity is the reversion rate for a series of well-characterized mutations in the Salmonella reversion rate bacteria. bacteria. BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez ©2013 BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez 5 Mutations and Cancer Mutations Kathi Shull Program Program Coordinator, UC Davis Internship and Career Center and Succumbed to Succumbed colon cancer, May 22, 2013 May BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez ©2013 BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez 6 p53 Protein and Cancer p53 DNA binding protein p53 (53 kDal) is a eukaryotic DNA binding protein. In humans it’s encoded by the TP53 gene. p53 is called the “guardian of the genome” because of its role in preserving genome integrity by preventing mutations from propagating from one cell to the subsequent daughter cells. Because of its role in monitoring DNA damage and cell cycle control, p53 acts as a tumor suppressor by preventing cancer. p53 mutations are the most common events observed in colorectal cancer, along with aneuploidy and rapid cell proliferation BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez ©2013 BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez 7 Mutation and Cancer Progression Metastatic Cells Mutation Mutation Genomic Plasticity Drug Resistant Metastatic Cells Primary Cancer Normal Cells Benign tumor BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez ©2013 BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez 8 p53 Pathway DNA Damage Cell Cycle Abnormalities Hypoxia Phosphorylation mdm2 Cell Cycle Arrest p53 p53 Apoptosis (programmed cell dead) DNA Repair C...
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