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Chapter 15: Controls over Genes. Skin Cancer. Basal Cell Carcinoma Squamous Cell Carcinoma Malignant Melanoma. Changes in DNA Trigger Cancer. Ultraviolet radiation can cause breaks Can promote formation of dimers. Controlling the Cell Cycle. Cycle has built-in checkpoints
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Skin Cancer Basal Cell Carcinoma Squamous Cell Carcinoma Malignant Melanoma
Changes in DNA Trigger Cancer • Ultraviolet radiation can cause breaks • Can promote formation of dimers
Controlling the Cell Cycle • Cycle has built-in checkpoints • Proteins monitor chromosome structure, whether conditions favor division, etc. • Proteins are products of checkpoint genes • Growth factors
Oncogenes • Have potential to induce cancer • Mutated forms of normal genes • Can form following insertions of viral DNA into DNA or after carcinogens change the DNA
Cancer Characteristics • Plasma membrane and cytoplasm altered • Cells grow and divide abnormally • Weakened capacity for adhesion • Lethal unless eradicated
Apoptosis • Programmed cell death • Signals unleash molecular weapons of self-destruction • Cancer cells do not commit suicide on cue
Gene Control Which genes are expressed in a cell depends upon: • Type of cell • Internal chemical conditions • External signals • Built-in control systems
Regulatory Proteins Can exert control over gene expression through interactions with: • DNA • RNA • New polypeptide chains • Final proteins
Control Mechanisms • Negative control • Regulatory proteins slow down or curtail gene activity • Positive control • Regulatory proteins promote or enhance gene activities
Chemical Modifications DNA wound around histone spool unwound DNA region Fig. 15-2a, p.232
Controls in Eukaryotic Cells NUCLEUS CTYOPLASM translational control protein product pre-mRNA transcript mRNA mRNA DNA transport processing control mRNA transport control mRNA degradation control protein product control transcription control inactivated mRNA inactivated protein Fig. 15-3, p.233
Controls in Eukaryotic Cells • Control of transcription • Transcript processing controls • Controls over translation • Controls following translation
Chromosome Puff • Portion of the chromosome in which the DNA has loosened up to allow transcription • Appears in response to ecdysone • Translation of transcripts from puffed region produces protein components of saliva
X Chromosome Inactivation • One X inactivated in each cell of female • Creates a “mosaic” for X chromosomes • Governed by XIST gene
X Chromosome Inactivation • A condensed X chromosome (Barr body) in the somatic cell nucleus of a human female Fig. 15-4a, p.234
Most Genes Are Turned Off • Cells of a multicelled organism rarely use more than 5-10 percent of their genes at any given time • The remaining genes are selectively expressed
Phytochrome • Signaling molecule in plants • Activated by red wavelengths, inactivated by far-red wavelengths • Changes in phytochrome activity influence transcription of certain genes
petal carpel stamen sepal Fig. 15-6, p.235
B A C 1 2 3 4 petals carpel sepals stamens Fig. 15-6, p.235
Homeotic Genes • Occur in all eukaryotes • Master genes that control development of body parts • Encode homeodomains (regulatory proteins) • Homeobox sequence can bind to promoters and enhancers
Knockout Experiments • Prevent a gene’s transcription or translation • Differences between genetically engineered knockout individuals and wild-type individuals point to function of knocked out gene • Knockout experiments shed light on genes that function in Drosophila development
Knockout Experiments Fig. 15-7a, p.236
Knockout Experiments Fig. 15-7b, p.236
Knockout Experiments Fig. 15-7c, p.237
Body Plan A7 A5 A3 A1 T2 T2 T2 A8 A4 A2 T3 T1 T2 A5 A6 A7 A8 A4 A3 A2 A1 Md T3 Mx T1 T2 Lb A8 A7 A6 T1 T2 A4 A3 A1 T3 A2 A5 A4 A3 A2 T1 T3 A1 T2 A6 A7 A8 Fig. 15-8a, p.237
Body Plan Fig. 15-8b, p.237
Body Plan Fig. 15-8c, p.237
Gene Control in Prokaryotes • No nucleus separates DNA from ribosomes in cytoplasm • When nutrient supply is high, transcription is fast • Translation occurs even before mRNA transcripts are finished
The Lactose Operon operator regulatory gene gene 1 gene 2 gene 3 operator transcription, translation promoter lactose operon repressor protein Fig.15-10, p. 241
Low Lactose • Repressor binds to operator • Binding blocks promoter • Transcription is blocked Fig.15-10, p. 241
High Lactose allolactose lactose mRNA RNA polymerase gene 1 operator promoter operator Fig.15-10, p. 241
CAP Exerts Positive Control • CAP is an activator protein • Adheres to promoter only when in complex with cAMP • Level of cAMP depends on level of glucose
Positive Control – High Glucose • There is little cAMP • CAP cannot be activated • The promoter is not good at binding RNA polymerase • The lactose-metabolizing genes are not transcribed very much
Positive Control – Low Glucose • cAMP accumulates • CAP-cAMP complex forms • Complex binds to promoter • RNA polymerase can now bind • The lactose-metabolizing genes are transcribed rapidly
Hormones • Signaling molecules • Stimulate or inhibit activity in target cells • Mechanism of action varies • May bind to cell surface • May enter cell and bind to regulatory proteins • May bind with enhancers in DNA
Polytene Chromosomes • Occur in salivary glands of midge larvae • Consist of multiple DNA molecules • Can produce multiple copies of transcripts
Vertebrate Hormones • Some have widespread effects • Somatotropin (growth hormone) • Others signal only certain cells at certain times • Prolactin stimulates milk production