Lecture 1-DNA Structure (Rosenthal)

Question 1

DNMT1

Answer 1

sister strand methylation

Question 2

DNMT3B (or A) When do you see this expressed?

Answer 2

• de novo methylation
• early in development
  NOTE: this family is a group of paralogs, all found on different chromosomes

Question 3

ICF

Answer 3

disease resulting from a mutation in DNMT3B

Question 4

What does it mean if a nucleotide is exo or endo? (Puckered formations)

Answer 4

• this has to do with whether the C2 or C3 is in the plan of the base
• exo: C2 or C3 is NOT in the plane of the base
• endo: C2 or C3 is in the plane of the base

Question 5

Z DNA form is assumed when ______

Answer 5

the DNA is in a left handed turn, highly methylated

Question 6

How much of human DNA is genes?

Answer 6

30% (1.5% exons)

Question 7

How much of the DNA is transposons?

Answer 7

45%

Question 8

What’s the most defining feature of ICF?

Answer 8

• loss of methylation from centromeric and pericentromeric regions of DNA
• inability of chromosomes to condense during mitosis
• subcellular distribution of chromatin proteins
• NOTE: physical manifestations include immunodeficiency, facial abnormalities, mental retardation

Question 9

Which chromosomes are more affected in ICF?

Answer 9

• 1
• 9
• 16

Question 10

What is special about the histones at the centromeres?

Answer 10

marked by an H3 variant

Question 11

Where are most minisatellies found?

Answer 11

sub-telomeric region (90%)

Question 12

What does H3 do?

Answer 12

It has a long branch that acts like a sensor for the environment and can transduce signals

Question 13

What does H1 do?

Answer 13

• Compaction: responsible for solenoid structure (6 nucleosomes creating the cross section of 30nm fiber)
• holds DNA to chromosomes

Question 14

Mitogenic H3 Kinases

Answer 14

phosphorylate H3 (10) to promote acetylation (9, 14) of H3 during interphase

Question 15

Mitotic H3 kinases

Answer 15

• phosphorylate H3 (10, 28) to condense it for mitosis

Question 16

Cohesins

Answer 16

• on chromosomes, tether chromatids together for replication

Question 17

Condensins

Answer 17

keep chromatids in a condensed state

Question 18

What proteins promote deacetylation (in order)?

Answer 18

• DNMT3B
• MeCP2
• Class 1: HDAC1,2,8

Question 19

What proteins promote acetylation?

Answer 19

• P90rsk2: RSK family of kinases (ribosomal S6 kinase family), phosphorylates S10 of H3
• CREB-binding Protein (CBP): HAT

Question 20

Histone acetylation decreases chromatin affinity for _____

Answer 20

H1

Question 21

Rett Syndrom from a mutation in ____

Answer 21

MeCP2–X DOMINANT–RARE!

Question 22

Rett Syndrome usually affects

Answer 22

females, males usually die

Question 23

Coffin-Lowry syndrome is a mutation in_____ and what is its hereditary style?

Answer 23

• RSK2

- X-linked Dominant

Question 24

Rubenstein Taybi syndrome is a mutation in _____ and has what inheritance style?

Answer 24

• CBP

- Autosomal Dominant

Question 25

Which diseases result in chromatin that can’t condense?

Answer 25

• ICF (DNMT3B)

- Rett syndrome (MeCP2)

Question 26

Which diseases result in chromatin that can’t decondense?

Answer 26

• Coffin-Lowry Syndrome

- Rubenstein-Taybi Syndrome