13BIS101S2013GeneRegulLect13-1

P53 is crucial in multicellular organisms where it

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Unformatted text preview: guez ©2013 BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez 44 The Protein GAL4 Structure GAL4 is a 99kDal (881 amino acid) metalloprotein with two Zn ions bound in a zincGAL4 zincfinger. GAL4 acts as a dimer and the zinc finger of each monomer binds to the GAL4 zinc major groove in the UASs. GAL4 has two separate binding domains, one for GAL80 and one for the UAS. The GAL80 binding site on GAL4 is also the binding site for TBF. Although GAL80 blocks GAL gene transcription, it does not bind DNA like the lac repressor. lac Gal 80 binding site UAS binding sites p53 DNA binding protein BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez ©2013 BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez 45 p53 Protein and Cancer p53 (53 kDal) is a tumor suppressor protein that in humans, is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer. As such, p53 has been described as "the guardian of the genome” because of its role in conserving genome integrity by preventing the propagation of mutations for one cell to the subsequent daughter cells. p53 DNA binding protein BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez ©2013 BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez 46 Proposed GAL4 — Cys6 Zinc Finger Lys+ Glu Lys+ Ser Pro Lys+ Cys Cys Lys+ Zn Leu Ala Lys+ Lys+ Cys Lys+ Leu Leu Asn Arg+ Cys Ile Asp NH2 Ala Cys Asn Zn Trp Glu Cys Arg+ BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez ©2013 BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez COOH 47 Comparing Lac and Gal Gene Regulation Lactose Operon Multiple genes regulated Polycistronic mRNA Regulation responsive to changes Regulation in external chemical environment in Negative control by repressor Repressor acts as a Repressor homotetramer homotetramer Repressor binds operator DNA Repressor sequence sequence Operator sequence is palindromic Inducer molecule (allolactose) Inducer inactivates repressor inactivates Positive control by catabolite Positive activation protein (CAP) activation Repression of CAP by a glucose Repression catabolite that reduces cAMP levels levels Galactose Gene Regulation Multiple genes regulated Monocistronic mRNAs Regulation responsive to changes Regulation in external chemical environment in Negative control by GAL80 GAL80 acts as a dimer GAL80 binds GAL4, not UAS GAL80 DNA sequences DNA UAS sequences are palindromic Inducer molecule (galactose) Inducer blocks GAL80 through GAL3 binding binding Positive control by GAL4 dimer Repression of GAL4 by a Repression glucose-induced, catabolite repressor protein (CRP) repressor BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez ©2013 BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez 48 Example of Gene Regulation in Humans Fetal hemoglobin γ turns off after birth and is replaced by the adult hemoglobin, β BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez ©2013 BIS101­001, Spring 2013—Genes and Gene Expression R.L. Rodriguez 49...
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