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MHG 1 > DNA I & II > Flashcards

DNA I & II Flashcards

1
Q

Nucleotides

A

A = T

G Ξ C

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2
Q

Methylation of nucleotides

A
  1. Occurs at CG regions
  2. De novo: DNMT3A & DNMT3B
  3. Maintenance: DNMT1
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3
Q

B form of DNA

(4)

A
  1. 3.4Å btwn bases
  2. 10.5 bases per turn
  3. Inside is hydrophobic; bases tightly packed
  4. Right handed corkscrew
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4
Q

DNA structure: important angles (2)

A
  1. Angle 7: syn or anti

*Cytidine can only do anti due to steric hindrance of carbonyl

  1. Angle 4: C-2’ or C-3’ will be “puckered”

endo and exo

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5
Q

A form of DNA

(5)

A
  1. Shorter and fatter
  2. Right handed helix
  3. RNA-RNA or RNA-DNA
  4. 11 bases per turn
  5. Protect bacteria when phosphorylated

*In bacteria, UV damage causes pyrimidine dimers (bad)

Conversion of B–> A form by small acid soluble proteins protects DNA from damage by moving adjacent Thymines away from each other

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6
Q

Z form of DNA

(6)

A
  1. Longer and skinnier
  2. Left handed helix
  3. Proteins bind to change B —> Z form
  4. Contains many CG regions and methyl-CG
  5. 12 bases per turn
  6. Reders gene txn inactive = silencing
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7
Q

Simple sequence repeats

(2 examples)

A

Satellite DNA, minisatellite DNA, microsatellite DNA

  1. Centromeres: place of attachment for MT. Critical for proper segregation. Marked by histon H3 variant
  2. Telomeres: Protects genes on ends; provides mechanism for replication of ends of chromosome

*Get shorter every time cell divides

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8
Q

Nucleosomes & Histones

(4)

A
  1. complex of 8 histones (H2A, H2B, H3, H4) + DNA =solenoid
  • Each histone contains 2 domains; cross section shows a 4 helix fold interaction
  • Rich in Lys and Arg (+) to interact w/ phosphate groups on DNA backbone
  1. When wrapping around histone, DNA has to be underwound by topoisomerase by 5%
  2. Nucleosome is critical for compaction: condenses DNA by 7%
  3. Roles
  • H3: acts as a receptor for signaling
  • H1 (linker): allows for compaction into 30nm fiber. 6 H1 interact to form circle
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9
Q

Chromosomal organization

A
  1. Naked DNA (2nm) *Txn Active
  2. Nucleosome (10nm) 7x *Txn Active
  3. 30nm fiber (30) 40-100x
  4. Nuclear scaffold 1000x
    * Main form during interphase
  5. chromatin condensed 10,000x
  • heterochromatin
  • or during mitosis
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10
Q

Histone modifications

(3)

A

Acetylation, methylation, phosphorylation, ubiquitinylation

  1. Histone acetyltransferase (HAT): acetylates Lysines CREB-binding protein (CBP)
  • removes + charge –> looser binding –> TRANSCRIPTIONALLY ACTIVE
  • Acetylation also decreases chromatin affinity to H1, weaken interaction

*p90rsk2: phosphorylates Ser10 on H3 and recruit HAT

  1. Histone deactylase (HDAC 1, 2, 8): removes acetyl grp
    * Restores condensation –> TRANSCRIPTIONALLY INACTIVE
  2. Methylation –> TRANSCRIPTIONALLY INACTIVE
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11
Q

DNA modifications

(3)

A
  1. Cohesin & Condensins –> global compaction
  2. DNA methyltransferases (DNMT1 and 3AB) –> TRANSCRIPTIONALLY INACTIVE
  • Promoter regions containing high amounts of methylated CpG regions
  • Methylation of heterochromatin = low levels of gene expression
  • _Methyl groups attract HDACs that maintain gene inactivation _
  1. Methyl CpG binding proteins (MeCP2) –> TRANSCRIPTIONALLY INACTIVE
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12
Q

Immunodeficiency-centromeric Instability-Facial anomalies syndrome

ICF syndrome

(4)

A

DNA METHYLATION: CHROMATIN REPRESSION

  1. Autosomal recessive
  2. Instability of pericentromeric heterochromatin 1, 9, 16 due to deficiency in DNMT3B
  3. Misexpression of key genes cause: mental retardation and developmental delay; perturb cranio-facial, cerebral, and immunological development
  4. Constitutive hypomethylation of satellite 2 DNA –> decreased condensation & centromeres not compact–> chromosome breakage
    * Subcellular distribution of chromatin proteins is altered
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13
Q

Rett syndrome (RTT)

(3)

A

DNA METHYLATION: CHROMATIN REPRESSION

  1. Females; recognized in infancy; blood test confirmation
  2. Decelerated head growth, loss of speech and hand use, repetitive hand movements
  • Sometimes autism, apraxia, breathing dysfunction
  • Affects NT & growth factors
  1. Caused from mutations in MeCP2 on X chromosome
  • Restoring levels of protein relieves symptoms
  • try to activate silent MeCP2 on inactive X
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14
Q

Coffin-Lowry Syndrome

(2)

A

HISTONE PHOSPHORYLATION: CHROMATIN ACTIVATION

  1. Mutations in RSK2
  2. Facial dysmorphism, skeletal deformation, abnormal digits
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15
Q

Rubenstein-Taybi Syndrome

(4)

A

_HISTONE ACETYLATION: CHROMATIN ACTIVATION _

  1. Haploinsufficiency of CBP fxn (HAT)
  2. Autosomal dominant
  3. mental retardation, cardiac, nose, thumb
  4. Facial abnormalities
  5. Skeletal abnormalities b/c CBP is a txn coactivator for BMPs (bone morphogenic proteins)
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MHG 1 (10 decks)

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