Topic B: The Structure and Transmission of Genetic Information Flashcards
Briefly define chromosome territories and compartments.
The DNA in each chromosome occupies a defined volume of the nucleus and only overlaps with its immediate neighbors. Chr territories (CT) are irregular but typical 1 to 2 micrometers in diameter, and consists of smaller subdomains. They have been found to border each other closely, neighboring chromosomes can invade each others CT and intermingle at their peripheries. Observations of living cells have also revealed that chr are essentially immobile most likely held in place by the force exerted upon them by their neighbors. CT are semi conserved from parent to daughter cell during cell devision, with locations in the daughter cell similar to those in the parent cell.
List 2 regulated covalent modifications that affect chromatin structure and describe their effects.
DNA Methylation – condenses chromatin and silences the region Histone Acetylation – opens chromatin and typically correlated with active regions of genome
Define epigenetics
Heritable changes in phenotype or gene expression, and caused by mechanisms other than changes in the underlying DNA sequence.
Name two epigenetic marks that affect gene expression.
H3K4me3, H3K9me, and H3K27me3
Give 3 examples of epigenetic modifications. How do they differ from DNA mutations?
DNA methylation, Histone acetylation, and Histone methylation
Difference: they are Reversible. The acetylation/deacetylation of histones is often used as part of control of gene expression. DNA mutations can be corrected via mismatch repair but are typically not used as a reversible regulatory mechanism. Epigenetic modification do not change the nucleotides – instead they can change the conformation of the chromatin structure, etc.
Describe 2 distinct mechanisms by which a chromosomal translocation can result in activation of a proto-oncogene.
The promoter and/or enhancer of a housekeeping gene translocation upstream a proto-oncogene can activate constitutively. miRNA expression which typically inhibits translation of target proto-oncogene may be disrupted.
Give two examples of different mechanisms that produce genomic alterations in cancers.
- ) Nearby regulatory DNA sequences causes normal protein to be overproduced
- ) fusing to actively transcribed gene produces hyperactive fusion protein
Other ways of saying the same thing that we had put down previously:
- ) If the gene moves into a region of the genome that is highly transcribed
- ) If the gene moves into a region under the control of a strong enhancer
- ) gene fusions
What kinds of cellular and chromosomal changes would you expect to see if telomeres failed to function properly? Why?
cellular changes: apoptosis
chromosomal changes: non-homologous chromosome ends might fuse because they are no longer capped because they would be detected as a double stranded break, Could form circular chromosomes for the same reasons as above, If the telomeres fail to shorten (or are elongating) the cell would keep dividing
The human chromosomes and the chimp chromosomes have nearly the same karyotype except for human chromosome 2, which is a fusion of chimp chromosome 2A and 2B. In a bizarre experiment, soviet scientist Ilya Ivanovish attempted to create human-chimp hybrid. A. If such hybrid were to be made, would the resulting progeny be viable? Give a brief argument for why it should or should not be viable. B. If the hybrid were viable, what are the possible chromosomal segregation results of gametes pro-duced from such a hybrid? (focus on the chromosome 2/2A/2B only).
Looks like an open question. The Ilya’s experiments eventually failed. So the progeny probably is not viable because the different number of chromosomes, so the cells can not divide probably. [Some-how trisomy 21 patients sometimes can survive] The gametes could be (1)(2,2A,2B) and (none) (2) (2,2A) and (2B) (3) (2) and (2A,2B) (4) (2,2B) and (2A)
You are working on a yeast strain that keep giving rise to spontaneous mutations. You suspect that this is a mutater strain that is defective in a DNA repair pathway. Given that you have access to all commonly used mutagens, how would you determine whether the strain is defective in MGMT repair, nucleotide excision repair, or mismatch repair?
MGMT = methyl guanine methyl transferase
You can rule out nucleotide excision repair by exposing to UV and if thstrain i smuch less viable than the WT but acts the same as WT when exposed to different mutagens then it is prob a mutation in this pathway
You can rule out mismatch repair by doing the same but instead of UV you use alkylating agents, as they are sensitive to those.
What are the major components of the cell cycle?
M-> G1 -> S ->G2 -> m
M: mitosis is where sister chromatids separate and divide it
metaphase checkpoint
Interphase: G1 , S, G2
G1: Gap1 is cell growth and cells that cease division arrest
G1/S check point
S phase: DNA synthesis
G2: Gap 2 Cell growth
Describe the enzymatic activity of a cyclin-dependent kinase (Cdk) and what do they regulate?
CDKs regulate the cell ccycle. CDKs bind to cyclins which are regulatory proteins . Without cyclin, CDK has little kinase activity, but the cyclin-CDK complex is an active kinase. CDKs are serine-threonine kinases, as they phosphorylate their substrates on serines and threonines. Cyclin binding induces a conformation change that reveals Thr160 residue. Phosphorylation of Thr160 by CAK (CDK activating kinase) activates and stabilizes it. CDK activity is inhibited by phosphorylation of Try15 by Wee1. Dephosphorylation of Tyr15 by Cdc25 activates it.
Briefly describe how Cdk activity changes during exit from mitosis and how this change is controlled.
Cdk activity decreases through cyclin degradation. MPF (maturation promoting factor) which is made up of cyclinB and Cdk1 must be activated to enter mitosis and must be inhibited to exit mitosis. Cyclins are synthesized and degraded with the cell cycle. They are degraded by ubiquitin dependent pathway by APC (anaphase promoting complex,E3 ligase)
What mediates the destruction of cyclins during the cell cycle phase?
Ubiquitin-mediated proteolysis used to degrade cyclins, and this provides irreversible directionality.
What are checkpoints?Describe two examples of the consequence of defective checkpoint function.
Checkpoints are major events in the cell cycle that determine whether or not to proceed with the cell cycle.
Example 1. Start or restriction checkpoint between G1 and S decided whether or not to replicate the chr
A defective checkpoint can result in a chr not finished undergoing DNA repair to replicate, which will result in chrosomal abberations or inherited mutations.
Example 2. Metaphase checkpoint ensures all chromosomes are lined up at the plate and are ready to undergo anaphase. Consequence of defect in non-dis-junction that results in aneuploidy or abnormal number of chr in gametes.
