Topics Concept 8.5: Regulation of enzymes: What is an allosteric regulator? What are some examples? How do they benefit an organism Concept 12.1: What is the relationship between a chromosome and DNA? Why do cells divide? Why do chromosomes replicate? Concept 12.3: How is the cell cycle regulated? Why is the cell cycle regulated? Concept 18.1: How do bacteria (prokaryotes) use operons to regulate the expression of genes? What is the benefit of controlling gene expression to a bacteria? Concept 18.2: How do eukaryotes (like us) control gene expression? Know transcription factors, RNA processing Figure 18.18: Why don’t all cells end up the same, especially given that they have the same genetic code? Figure 18.23: How can mistakes in the control mechanisms of gene expression lead to cancer? Relate this figure to the BCR-ABL transcription factor translocation that results in Chronic Myeloid Leukemia. Negative and Positive Feedback Essential Knowledge 2.e.2: 2.e.3 3.b.1: 3.b.2: 4.c.2

Warm-UP: Check out this cool root tip! 1.How do you think the cells compare in different parts of the root? 2.What might regulate the cells ability to be different in different places? DUE Tomorrow: Lab Handout: Comparing Mitosis UNIT 7/8 TEST: This Thursday (see website for Test Review) Inheritance and Regulation DUE NOW: Stamp Sheet

Unit 8: Regulation Big Idea: Many biological processes involved in growth, reproduction, and homeostasis are dependent on regulation. Big Idea: Many biological processes involved in growth, reproduction, and homeostasis are dependent on regulation. Model: Chronic Myeloid Leukemia (CML), a type of blood cancer. Normally, the cell cycle is regulated so that cell death (apoptosis) and cell growth (mitosis) are balanced. In cancer, mutations affect gene expression by dys- regulating transcription factors, which in turn lead to changes in enzyme regulation of the cell cycle and subsequent tumor growth. Model: Chronic Myeloid Leukemia (CML), a type of blood cancer. Normally, the cell cycle is regulated so that cell death (apoptosis) and cell growth (mitosis) are balanced. In cancer, mutations affect gene expression by dys- regulating transcription factors, which in turn lead to changes in enzyme regulation of the cell cycle and subsequent tumor growth. Big Idea: Many biological processes involved in growth, reproduction, and homeostasis are dependent on regulation. Big Idea: Many biological processes involved in growth, reproduction, and homeostasis are dependent on regulation. Model: Chronic Myeloid Leukemia (CML), a type of blood cancer. Normally, the cell cycle is regulated so that cell death (apoptosis) and cell growth (mitosis) are balanced. In cancer, mutations affect gene expression by dys- regulating transcription factors, which in turn lead to changes in enzyme regulation of the cell cycle and subsequent tumor growth. Model: Chronic Myeloid Leukemia (CML), a type of blood cancer. Normally, the cell cycle is regulated so that cell death (apoptosis) and cell growth (mitosis) are balanced. In cancer, mutations affect gene expression by dys- regulating transcription factors, which in turn lead to changes in enzyme regulation of the cell cycle and subsequent tumor growth.

The cell cycle is regulated so that cell death (apoptosis) and cell growth (mitosis) are balanced. Cell cycle Mitotic (M) phase: mitosis and cytokinesis Interphase accounts for 90% of the cell cycle G1: growth S: DNA Replication (making sister chromatids) G2: growth Checkpoints: Finish M phase? – The Go Signal! Regulatory Proteins transcription factor (TF): Cyclin enzyme that regulates the TF: Cyclin-Dependent Kinase (Cdk) Stop and Enter G 0 : Leaving the cell cycle – G 0 : protein that gets built: MPF (maturation-promoting factor) cell differentiation: one cell becomes different than another because different genes are expressed Maturation: cell expresses traits depending on what type of cell it is

The cell cycle is regulated so that cell death (apoptosis) and cell growth (mitosis) are balanced. Cell cycle Mitotic (M) phase: mitosis and cytokinesis Interphase accounts for 90% of the cell cycle G1: growth S: DNA Replication (making sister chromatids) G2: growth Checkpoints: Finish M phase? – The Go Signal! Regulatory Proteins transcription factor (TF): Cyclin enzyme that regulates the TF: Cyclin-Dependent Kinase (Cdk) Stop and Enter G 0 : Leaving the cell cycle – G 0 : protein that gets built: MPF (maturation-promoting factor) cell differentiation: one cell becomes different than another because different genes are expressed Maturation: cell expresses traits depending on what type of cell it is

S G1G1 M checkpoint G2G2 M Control system G 1 checkpoint G 2 checkpoint The cell cycle is regulated so that cell death (apoptosis) and cell growth (mitosis) are balanced. Cell cycle Mitotic (M) phase: mitosis and cytokinesis Interphase accounts for 90% of the cell cycle G1: growth S: DNA Replication (making sister chromatids) G2: growth Checkpoints: Finish M phase? – The Go Signal! Regulatory Proteins transcription factor (TF): Cyclin enzyme that regulates the TF: Cyclin-Dependent Kinase (Cdk) Stop and Enter G 0 : Leaving the cell cycle – G 0 : protein that gets built: MPF (maturation-promoting factor) cell differentiation: one cell becomes different than another because different genes are expressed Maturation: cell expresses traits depending on what type of cell it is

The cell cycle is regulated so that cell death (apoptosis) and cell growth (mitosis) are balanced. Cell cycle Mitotic (M) phase: mitosis and cytokinesis Interphase accounts for 90% of the cell cycle G1: growth S: DNA Replication (making sister chromatids) G2: growth Checkpoints: Finish M phase? – The Go Signal! Regulatory Proteins transcription factor (TF): Cyclin enzyme that regulates the TF: Cyclin-Dependent Kinase (Cdk) Stop and Enter G 0 : Leaving the cell cycle – G 0 : protein that gets built: MPF (maturation-promoting factor) cell differentiation: one cell becomes different than another because different genes are expressed Maturation: cell expresses traits depending on what type of cell it is

1.Focus on one field of view “in the middle” of the root cap 2.Focus at 400X 3.Count ALL cells in interphase. Count ALL cells in mitosis. 4.Calculate % difference 5.Change field of view, but stay “just behind” the root cap. Repeat steps #2-4 6.Repeat #1-5, but move to the “end” (notice, there is a “cap” in front of the end) Lab: Cell Division Regulation in Onion Roots “cap”

Warm-UP: What is cancer? Why is cancer so hard to cure? What treatments do you know of? DUE NOW: Lab Handout: Comparing Mitosis in Onion Cells UNIT 7/8 TEST: This Thursday (see website for Test Review) Inheritance and Regulation

The cell cycle is regulated so that cell death (apoptosis) and cell growth (mitosis) are balanced. Cell cycle Mitotic (M) phase: mitosis and cytokinesis Interphase accounts for 90% of the cell cycle G1: growth S: DNA Replication (making sister chromatids) G2: growth Checkpoints: Finish M phase? – The Go Signal! Regulatory Proteins transcription factor (TF): Cyclin enzyme that regulates the TF: Cyclin-Dependent Kinase (Cdk) Stop and Enter G 0 : Leaving the cell cycle – G 0 : protein that gets built: MPF (maturation-promoting factor) cell differentiation: one cell becomes different than another because different genes are expressed Maturation: cell expresses traits depending on what type of cell it is

In cancer, mutations affect gene expression by dys- regulating transcription factors which regulate enzymes. Cancer: dys-regulation of TFs of cell growth= more growth than death. Transcription Factors: (TFs) cell-type specific TFs: proteins that bind to DNA and start transcription can be regulated: turned on (activated) or off (inhibited) by enzymes binding to “allosteric site” Example: Chronic Myeloid Leukemia (CML) Normal: Regulation of Myeloid Cell Maturation –ABL gene  ABL enzyme  active TF for myeloid cell maturation to WBC Cancer: Dysregulation: myeloid cells do not enter G 0, but instead stay in the cell cycle –driven by a chromosomal translocation (Translocation of Chr22 onto end of Chr9 creating fusion gene of BCR and ABL (a kinase) –BCR-ABL gene  BCR-ABL enzyme  active TF for myeloid cell division –Result: leukemia overproliferation of undifferentiated, immature cells Anemic – low RBCs (chokes out growth of other blood cells) Low WBCs – prone to infection

In cancer, mutations affect gene expression by dys- regulating transcription factors which regulate enzymes. Cancer: dys-regulation of TFs of cell growth= more growth than death. Transcription Factors: (TFs) cell-type specific TFs: proteins that bind to DNA and start transcription can be regulated: turned on (activated) or off (inhibited) by enzymes binding to “allosteric site” Example: Chronic Myeloid Leukemia (CML) Normal: Regulation of Myeloid Cell Maturation –ABL gene  ABL enzyme  active TF for myeloid cell maturation to WBC Cancer: Dysregulation: myeloid cells do not enter G 0, but instead stay in the cell cycle –driven by a chromosomal translocation (Translocation of Chr22 onto end of Chr9 creating fusion gene of BCR and ABL (a kinase) –BCR-ABL gene  BCR-ABL enzyme  active TF for myeloid cell division –Result: leukemia overproliferation of undifferentiated, immature cells Anemic – low RBCs (chokes out growth of other blood cells) Low WBCs – prone to infection

In cancer, mutations affect gene expression by dys- regulating transcription factors which regulate enzymes. Cancer: dys-regulation of TFs of cell growth= more growth than death. Transcription Factors: (TFs) cell-type specific TFs: proteins that bind to DNA and start transcription can be regulated: turned on (activated) or off (inhibited) by enzymes binding to “allosteric site” Example: Chronic Myeloid Leukemia (CML) Normal: Regulation of Myeloid Cell Maturation –ABL gene  ABL enzyme  active TF for myeloid cell maturation to WBC Cancer: Dysregulation: myeloid cells do not enter G 0, but instead stay in the cell cycle –driven by a chromosomal translocation (Translocation of Chr22 onto end of Chr9 creating fusion gene of BCR and ABL (a kinase) –BCR-ABL gene  BCR-ABL enzyme  active TF for myeloid cell division –Result: leukemia overproliferation of undifferentiated, immature cells Anemic – low RBCs (chokes out growth of other blood cells) Low WBCs – prone to infection

In cancer, mutations affect gene expression by dys- regulating transcription factors which regulate enzymes. Cancer: dys-regulation of TFs of cell growth= more growth than death. Transcription Factors: (TFs) cell-type specific TFs: proteins that bind to DNA and start transcription can be regulated: turned on (activated) or off (inhibited) by enzymes binding to “allosteric site” Example: Chronic Myeloid Leukemia (CML) Normal: Regulation of Myeloid Cell Maturation –ABL gene  ABL enzyme  active TF for myeloid cell maturation to WBC Cancer: Dysregulation: myeloid cells do not enter G 0, but instead stay in the cell cycle –driven by a chromosomal translocation (Translocation of Chr22 onto end of Chr9 creating fusion gene of BCR and ABL (a kinase) –BCR-ABL gene  BCR-ABL enzyme  active TF for myeloid cell division –Result: leukemia overproliferation of undifferentiated, immature cells Anemic – low RBCs (chokes out growth of other blood cells) Low WBCs – prone to infection

Cancer: dys-regulation of TFs of cell growth= more growth than death. Transcription Factors: (TFs) cell-type specific TFs: proteins that bind to DNA and start transcription can be regulated: turned on (activated) or off (inhibited) by enzymes binding to “allosteric site” Example: Chronic Myeloid Leukemia (CML) Normal: Regulation of Myeloid Cell Maturation –ABL gene  ABL enzyme  active TF for myeloid cell maturation to WBC Cancer: Dysregulation: myeloid cells do not enter G 0, but instead stay in the cell cycle –driven by a chromosomal translocation (Translocation of Chr22 onto end of Chr9 creating fusion gene of BCR and ABL (a kinase) –BCR-ABL gene  BCR-ABL enzyme  active TF for myeloid cell division –Result: leukemia overproliferation of undifferentiated, immature cells Anemic – low RBCs (chokes out growth of other blood cells) Low WBCs – prone to infection In cancer, mutations affect gene expression by dys- regulating transcription factors which regulate enzymes.

Cancer: dys-regulation of TFs of cell growth= more growth than death. Transcription Factors: (TFs) cell-type specific TFs: proteins that bind to DNA and start transcription can be regulated: turned on (activated) or off (inhibited) by enzymes binding to “allosteric site” Example: Chronic Myeloid Leukemia (CML) Normal: Regulation of Myeloid Cell Maturation –ABL gene  ABL enzyme  active TF for myeloid cell maturation to WBC Cancer: Dysregulation: myeloid cells do not enter G 0, but instead stay in the cell cycle –driven by a chromosomal translocation (Translocation of Chr22 onto end of Chr9 creating fusion gene of BCR and ABL (a kinase) –BCR-ABL gene  BCR-ABL enzyme  active TF for myeloid cell division –Result: leukemia overproliferation of undifferentiated, immature cells Anemic – low RBCs (chokes out growth of other blood cells) Low WBCs – prone to infection

In cancer, mutations affect gene expression by dys- regulating transcription factors which regulate enzymes. Cancer: dys-regulation of TFs of cell growth= more growth than death. Transcription Factors: (TFs) cell-type specific TFs: proteins that bind to DNA and start transcription can be regulated: turned on (activated) or off (inhibited) by enzymes binding to “allosteric site” Example: Chronic Myeloid Leukemia (CML) Normal: Regulation of Myeloid Cell Maturation –ABL gene  ABL enzyme  active TF for myeloid cell maturation to WBC Cancer: Dysregulation: myeloid cells do not enter G 0, but instead stay in the cell cycle –driven by a chromosomal translocation (Translocation of Chr22 onto end of Chr9 creating fusion gene of BCR and ABL (a kinase) –BCR-ABL gene  BCR-ABL enzyme  active TF for myeloid cell division –Result: leukemia overproliferation of undifferentiated, immature cells Anemic – low RBCs (chokes out growth of other blood cells) Low WBCs – prone to infection

In cancer, mutations affect gene expression by dys- regulating transcription factors which regulate enzymes. Cancer: dys-regulation of TFs of cell growth= more growth than death. Transcription Factors: (TFs) cell-type specific TFs: proteins that bind to DNA and start transcription can be regulated: turned on (activated) or off (inhibited) by enzymes binding to “allosteric site” Example: Chronic Myeloid Leukemia (CML) Normal: Regulation of Myeloid Cell Maturation –ABL gene  ABL enzyme  active TF for myeloid cell maturation to WBC Cancer: Dysregulation: myeloid cells do not enter G 0, but instead stay in the cell cycle –driven by a chromosomal translocation (Translocation of Chr22 onto end of Chr9 creating fusion gene of BCR and ABL (a kinase) –BCR-ABL gene  BCR-ABL enzyme  active TF for myeloid cell division –Result: leukemia overproliferation of undifferentiated, immature cells Anemic – low RBCs (chokes out growth of other blood cells) Low WBCs – prone to infection

In cancer, mutations affect gene expression by dys- regulating transcription factors which regulate enzymes. Cancer: dys-regulation of TFs of cell growth= more growth than death. Transcription Factors: (TFs) cell-type specific TFs: proteins that bind to DNA and start transcription can be regulated: turned on (activated) or off (inhibited) by enzymes binding to “allosteric site” Example: Chronic Myeloid Leukemia (CML) Normal: Regulation of Myeloid Cell Maturation –ABL gene  ABL enzyme  active TF for myeloid cell maturation to WBC Cancer: Dysregulation: myeloid cells do not enter G 0, but instead stay in the cell cycle –driven by a chromosomal translocation (Translocation of Chr22 onto end of Chr9 creating fusion gene of BCR and ABL (a kinase) –BCR-ABL gene  BCR-ABL enzyme  active TF for myeloid cell division –Result: leukemia overproliferation of undifferentiated, immature cells Anemic – low RBCs (chokes out growth of other blood cells) Low WBCs – prone to infection

Warm-UP: Predict a solution for CML. Remember competitive inhibitors for enzymes? (think flipping pennies with a tennis ball taped to your hand) UNIT 7/8 TEST: Tomorrow (see website for Test Review) Inheritance and Regulation

In cancer, mutations affect gene expression by dys- regulating transcription factors which regulate enzymes. Cure: Gleevac Drug that competitively inhibits Bcr-Abl enzyme by filling the substrate site so TF for cell division gene cannot be activated First Targeted therapy for cancer

In cancer, mutations affect gene expression by dys- regulating transcription factors which regulate enzymes. Brian Druker and Novartis Late 1990s Cure: Gleevac Drug that competitively inhibits Bcr-Abl enzyme by filling the substrate site so TF for cell division gene cannot be activated First Targeted therapy for cancer

In cancer, mutations affect gene expression by dys- regulating transcription factors which regulate enzymes. Homeostasis could not be maintained if a cell’s metabolic pathways were not tightly regulated Enzyme Regulators: switching on/off enzymes –bind to another part of an enzyme (the allosteric site), –cause an enzyme to change shape and changing the active site –can inhibit or activate –Example: Cell Cycle Regulation by cyclin, an allosteric activator –Example: Dys-Regulation of Cell Maturation by BCR-ABL Cure: Gleevac Drug that competitively inhibits Bcr-Abl enzyme by filling the substrate site so TF for cell division gene cannot be activated First Targeted therapy for cancer