Lecture 11

Question 0

What are the principle lesions that lead to chromosomal aberrations?

Answer 0

Double strand breaks

Question 1

Where are sister chromatids held together?

Answer 1

Centromere

Question 2

What effector do DSBs activate that then guide the cell towards either senescence or apoptosis?

Answer 2

p53

Question 3

What is nondisjunction?

Answer 3

When members of a chromosome pair fail to separate during anaphase of meiosis

Question 4

What does nondisjunction result in?

Answer 4

Gametes with an incorrect number of chromosomes

Question 5

What is chromothripsis?

Answer 5

Shattering of the chromosome into thousands of pieces

Question 6

What causes chromothripsis?

Answer 6

Massive double strand breaks, followed by rearrangements, reassembly, and fusion

Question 7

Chromothripsis is commonly associated with what two disorders?

Answer 7

Fanconi anaemia and colorectal cancer

Question 8

What is a pericentric inversion?

Answer 8

A single chromosome with two breaks swaps the location of its two fragments

Question 9

What is a paracentric aberration?

Answer 9

Both points of exchange lie on same side of centromere

Question 10

What are interchanges?

Answer 10

Exchange of two sister chromatids between separate chromosomes

Question 11

What is the Philadelphia Chromosome?

Answer 11

Mutated chromosome due to translocation between chromosomes 9 and 22

Question 12

What condition does the Philadelphia Chromosome cause?

Answer 12

Chronic myelogenous leukemia (CML)

Question 13

What chromosome aberration causes Burkitt Lymphoma?

Answer 13

Translocation between chromosomes 8 and 14

Question 14

What does the translocation between chromosomes 8 and 14 cause?

Answer 14

Translocation of MYC oncogene from chromosome 8 to the heavily expressed heavy chain IG gene region of chromosome 14

Question 15

What are epigenetics?

Answer 15

Heritable non-genetic modifications

Question 16

What are CpG islands?

Answer 16

Repeats of C and G where methylation control occurs

Question 17

Relative to the gene, where are CpG islands typically found?

Answer 17

Close to the start of the promoter

Question 18

What does methylation of the promoter do?

Answer 18

Prevents binding of transcription factors, thus inhibiting gene expression

Question 19

Is epigenetic methylation inheritable?

Answer 19

Yes

Question 20

In cancers, what genes are methylated?

Answer 20

Tumor suppressor genes

Question 21

In cancers, what genes are unmethylated?

Answer 21

Oncogenes

Question 22

What is a nucleosome?

Answer 22

DNA wrapped around a core of 8 histone proteins

Question 23

What protein locks the DNA around the histone complex?

Answer 23

Linker histone H1

Question 24

What is the epigenetic site of histone proteins?

Answer 24

N-terminal tails

Question 25

What are four types of histone modification?

Answer 25

Acetylation, methylation, phosphorylation, and ubiquitination

Question 26

What is heterochromatin?

Answer 26

Compact DNA clustered near nucleolus and nuclear membrane

Question 27

What is euchromatin?

Answer 27

Dispersed DNA that occupies most of the nuclear region

Question 28

In what kind of chromatin is transcription "on?"

Answer 28

Euchromatin

Question 29

What histone modification promotes transcription?

Answer 29

Acetylation

Question 30

What histone modification inhibits transcription?

Answer 30

Methylation

Question 31

What class of enzymes methylates DNA?

Answer 31

DNA methyltransferases

Question 32

How many DNA methyltransferases do humans have?

Answer 32

3

Question 33

Which is the "maintenance" methyltransferase responsible for copying methylation patterns during replication?

Answer 33

DNMT1 (methyltransferase 1)

Question 34

Ubiquitination is a form of ____

Answer 34

Post-translational modification

Question 35

Ubiquitin is found covalently bound to what amino acid residue?

Answer 35

Lysine

Question 36

What does ubiquitin regulate?

Answer 36

Protein degradation, cellular location, endocytic trafficking, histones

Question 37

What is the function of histone ubiquitin ligases (HULs)?

Answer 37

Add ubiquitin to histone complexes

Question 38

What notable oncogene is a part of the HUL?

Answer 38

BRCA1

Question 39

Loss of BRCA1 leads to a loss of what?

Answer 39

Histone ubiquitination

Question 40

What 2 conditions are caused by mutations in DNA sensing and signaling?

Answer 40

Fanconi anemia (FA) and ataxia-telangiectasia (AT)

Question 41

What 1 condition is caused by mutations in DNA topology?

Answer 41

Bloom syndrome (BS)

Question 42

What 4 conditions are caused by mutations in DNA repair?

Answer 42

Xeroderma pigmentosum (XP), Cockayne syndrome (CS), Trichothiodystrophy (TTD), and hereditary non-polyposis colon cancer (HNPCC/Lynch's Syndrome)

Question 43

What do HDAC inhibitors do?

Answer 43

Inhibit HDAC activity, increasing histone acetylation and gene transcription

Question 44

What do DNMT inhibitors do?

Answer 44

Block activity of DNMTs, decreasing histone methylation, increasing gene transcription