Log in
HomeClass Notes1,200,000CA670,000

Biology 1002B Lecture Notes - Lecture 17: Helix-Turn-Helix, Programmed Cell Death, Breast Cancer

31 views8 pages
sapphirebear815
15 Mar 2016
School
Western University
Department
Biology
Course
Biology 1002B
Professor
Tom Haffie

For unlimited access to Class Notes, a Class+ subscription is required.

Document Summary

Which of the following components of gene expression would be most likely to contain a. Helix-turn helix domain: cyclin-dependent kinase, translation release factor, laci gene product, enhancer region. Helix-turn helix are in protein not dna. Helix turn helix is dna-binding domain is the part of a protein that interacts with the dna. Helix turn helix are in the protein not in the dna that protein binds on to. They are not in the region that attracts the protein, but in the protein itself. Dna-binding proteins have those sequences in them. Protein domains, not places that proteins bind onto. Drosophila has to make a worm and a fly with their genome. Series of genes can be sequentially expressed to create a multi-nucleate egg to a larva to pupi to adult. Which of the following classes of genes would be the first to be expressed in the nuclei of. Drosophila zygotes: maternal effect genes, segmentation genes, homeotic genes, programmed cell death genes.

Get access

Grade+
$40 USD/m
Billed monthly
Grade+
Homework Help
Study Guides
Textbook Solutions
Class Notes
Textbook Notes
Booster Class
10 Verified Answers
Class+
$30 USD/m
Billed monthly
Class+
Homework Help
Study Guides
Textbook Solutions
Class Notes
Textbook Notes
Booster Class
7 Verified Answers

Related Documents

Biology 1002B Lecture Notes - Lecture 17: Programmed Cell Death, Mental Floss, Histone Deacetylase
ultramarinecrab393
Biology 1002B Lecture Notes - Lecture 14: Helix-Turn-Helix, Tata-Binding Protein, Leucine Zipper
blushyak979
Biology 1002B Lecture 17: LECTURE 17- CANCER
blushyak979

Related Questions

QUESTION 10

If you can drink milk as an adult, it means that you have inherited a mutation in the promoter of your lactase gene (the gene that encodes the enzyme you need to break down lactose). Predict the effect of this mutation:

The mutation changes the number of domains in the enzyme, which makes it work more efficiently

The mutation changes the amino acid sequence of the lactase protein

The mutation increases the number of copies of the lactase gene that will be found in your genome

The mutation changes whether the lactase sequence is found in an intron or exon

The mutation affects the expression of the lactase gene

1.2 points

QUESTION 11

A competitive inhibitor is decreasing the activity of an enzyme. Predict the effect of adding more substrate to the reaction.

The substrate will increase the reaction rate by binding to the allosteric site

The substrate will increase the reaction rate by competing with the inhibitor for the active site

The reaction rate will not change unless the inhibitor can be removed

The enzyme adjusts its shape so that the substrate, but NOT the competitive inhibitor, can bind

The substrate will bind to the competitive inhibitor and block its ability to bind to the enzyme

1.2 points

QUESTION 12

What determines where in the genome a transcription regulator will bind?

Transcription regulators bind to the 5' UTR region of a gene

Regulators bind via complementary base-pairing to certain DNA molecules

Covalent bonds form between the transcription regulator and the atoms of the DNA backbone

Every eukaryotic gene has a different transcription regulator that will bind to the 5' end of the gene

Transcription regulators bind to specific DNA sequences via multiple weak non-covalent interactions

1.2 points

QUESTION 13

What is the basic premise of cell theory?

DNA -> RNA -> protein

All cells arise from pre-existing cells

DNA provides the complete instructions to create a cell

The identity of a cell is determined through gene expression patterns

All cells contain the same four basic macromolecules

1.2 points

QUESTION 14

What is the benefit of using BOTH the lac activator and the lac repressor to control gene expression?

Using both an activator and repressor enables cells to more accurately determine the amount of lactose available in the environment

Enzymes to digest lactose are only made when energy is low and lactose is available

The activator can override the inhibition of the lac operon by the repressor

The repressor can control the enhancer, while the activator can control the promoter

When neither the lac activator or repressor is present, expression of the lac operon is too high

1.2 points

QUESTION 15

What is the histone code used for?

Phosphorylation and acetylation of DNA affect its ability to be compacted

Changes to the sequence of DNA change whether DNA will wrap around histone proteins

Covalent modifications of histones affect the ability of the transcription initiation complex to form

Histones provide the codon sequences needed for translation to occur

The histone code affects which amino acids will get added to a polypeptide

QUESTION 1

How is a bone marrow transplant able to treat someone with leukemia?

The donor blood contains antibodies that destroy cancer cells

Donor blood contains stem cells that regenerate cells in the immune system

Bone marrow contains induced pluripotent stem cells that turn into red blood cells

Bone marrow contains tumor supressor genes that slow down leukemia growth

Bone marrow contains pluripotent human embryonic stem cells

1.2 points

QUESTION 2

What would happen if siRNAs designed to target mRNA from an oncogene were introduced into cancer cells?

Increased genomic instability would result from adding foreign nucleic acids

New mutations would arise in the oncogene

The oncogene would be converted back into a proto-oncogene

The siRNAs would compete with the oncogene's active site

Production of the oncogene protein would decrease

1.2 points

QUESTION 3

What is the purpose of chromatin-remodeling enzymes in human cells?

The enzymes control the rate of translation of an mRNA transcript

The enzymes add phosphate or methyl groups to histone tails

The enzymes slide nucleosomes farther apart or closer to each other

The enzymes send damaged proteins to the proteasome for degradation

The enzymes cause DNA looping to occur

1.2 points

QUESTION 4

If you wanted to resurrect the mammoth, how would you do it?

Use somatic cell nuclear transfer to insert the mammoth genome into the egg of an elephant

Use transcription factors to re-program adult cells from elephants into mammoth cells

Change the gene expression patterns of elephants to increase production of mammoth genes

Use siRNAs to decrease expression of elephant-specific genes in an elephant embryo

1.2 points

QUESTION 5

How is eukaryotic transcription initiated?

RNA polymerase is recruited to the start codon by transcription factors

RNA polymerase begins transcription at the enhancer sequence

RNA polymerase is activated by binding to GTP

An initiator tRNA binds to the ribosome

A complex of proteins forms at the promoter of a gene

Read the summary and answer questions in bold below:

In this post, we’ll be focusing on Tyler Jacks and his graduate student Francisco J. Sánchez-Rivera’s review, “Applications of the CRISPR-Cas9 system in cancer biology,” circa 2015 in Nature Reviews. So we understand the context of the authors, Jacks is the director of the Koch Institute for Integrative Cancer Research at MIT. His lab has a large mouse experimental component (MIT 2017). This sets the stage for the angle we’ll be reading from. In all, it’s a nice roundup of his and colleagues' cancer applications of CRISPR-Cas9 with great graphics, but leaves a bit desired in crossing the bridge from mouse to human.

Briefly, the CRISPR-Cas9 system stems from the prokaryotic immune system, where the RNA-guided DNA endonuclease Cas9 uses a single guide RNA (sgRNA) containing a CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA) that binds Cas9 and directs it to the genomic sequence of interest, adjacent to a photospacer adjacent motif (PAM). Cas9 causes a precisely-directed double-stranded break (DSB) in the DNA, that gets repaired via non-homologous end joining (NHEJ) or homology-directed repair (HDR).

With NHEJ, this can disrupt the gene by creating Indels: frameshifts and stop codons. In cancer, individual oncogenes or tumor suppressors can be targeted, or drug response modulators, or synthetic lethality genes. With a multiplexed knockout approach, combinatorial vulnerabilities and epistatic relationships can be assessed.

For gene modification via HDR, target single or double-stranded DNA can be introduced, resulting in precise gene knock-ins, with potential effects of introducing point mutations to mimic cancers, fluorescent reporters/synthetic tags can be created, conditional (Cre-lox/Flp-FRT) constructs can used to turn off/on a mutation, non-coding elements like enhancers/insulators/promoters can turn on proto-oncogenes, and ultimately, HDR can be used for gene correction.

With Cas9 and 2 sgRNAs, there can be genomic rearrangements, leading to deletions, inversions (like EML4-ALK), and translocations (like BCR-ABL).

Dead Cas9 (dCas), which lacks its endonuclease activity via mutation to its HNH and RuvC domains, can be used for reversible, transcriptional repression or activation of coding and non-coding genes, or chromatin modification, via an effector.

Much of the practical applications of CRISPR-Cas9 is in ES cells and mouse models, both germinal and somatic (GEMMs and nGEMMs). With this technology, a plethora of GEMM/nGEMM models of cancer can be created, some with the ability to turn on/off the Cas9 system, and multiplexed sgRNAs can help gain further understanding of multi-hit cancers. Patient derived xenografts (PDX) mice can be assayed with CRISPR-Cas9 to determine different treatment efficacies. Entire libraries of sgRNA can be screened in cancer cell lines for enrichment/depletion with Cas9, and dCas9-activators/repressors can be used for complementarity, both of which providing insights into drug targets, synthetic lethality, and chemotherapy modulators.

The delivery mechanisms for the system are diverse, and include plasmids, lentivirus, adenovirus, nanoparticles, hydrodynamic gene transfer, and protein-based. The authors also cite integrating Cas9 into the GEMMs, so it’s one less thing needed in the delivery vehicle. This of course would not be applicable to human.

Ultimately, human cancer treatment is the goal. Yes, we know the boundaries between ES/mice experimental models and human embryos have already been broken, with an international team targeting the autosomal dominant mutation in MYBPC3, which causes cardiac myopathy (Ledford 2017). But the current compromise position of CRISPR-Cas9 technology toward therapeutics and treatment, beyond basic science understanding, is using primary cells, organoids, PDX, or personalized GEMMs to create genetic and drug screens.

In theory, what would it take to bring CRISPR-Cas9 to the ultimate, targeted gene therapy via either NHEJ or HDR, in human cancer? Are there cancers that are better bets for CRISPR-Cas9 than others, delivery vehicles that are safer or better optimized? Is CRISPR-Cas9 really “on target” enough to introduce into a person, and how do we best assess?