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MCM II > Functions and Dysfunctions of Genomic Regulation > Flashcards

Functions and Dysfunctions of Genomic Regulation Flashcards

1
Q

Purines

A

Adenosine and Guanine

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2
Q

Pyrimidines

A

Cytosine and Thymine

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3
Q

How many bonds between A and T

A

2

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4
Q

How many bonds between G and C

A

3

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5
Q

What is double stranded and anti-parallel

A

DNA

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6
Q

What are he basic unit of chromosome packing

A

Nucleosomes

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7
Q

Euchromatin

A

Lightly packed form of chromatin (DNA, RNA, and protein).

  • Highly enriched in genes
  • often (but not always) under active transcription
  • most active protein of genome
  • abouT 92% OF HUMAN GENOME IS EUCHROMATIC
  • remainder is heterochromatin
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8
Q

Heterochromatin

A

Very condensed chromatin-stains darkly throughout the cell cycle, even in interphase

  • thought to be late replicating and genetically inactive
  • highly concentrated at centromers and telomers
  • contains VERY FEW ACTIVE GENES
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9
Q

What is the position effect

A

Activity of a gene depend on relative position on chromosone

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10
Q

Will genes be actively espresses or silenced if located near heterochromatin

A

silenced

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11
Q

What information is found on chromosomes?

A

Genes - encoding proteins, encoding RNA molecules

-Reg information, “JUNK” DNA

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12
Q

How many chromosomes in the human genome

A

46, 2 pairs of 23.

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13
Q

What was the human genome project

A

sequence of the human genome. 3 billion nucleotides

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14
Q

How many genes in the human genome

A

26,000

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15
Q

What percent of the genome is responsible for codine

A

1.5 percent (in exons)

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16
Q

What do introns usually begin with and what do they end with?

A

[…GT] and end with [AG…]

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17
Q

Does histone deacetylation actively repress or promote gene expression

A

histone deacetylation actively represses gene expression

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18
Q

Does histone acetylation actively repress or promote gene expression

A

Histome acetylation actively promotes gene expression

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19
Q

What are types of PTMs on histone tails

A 
Methylation
acetylation
phosphorylation
ubiquitination
SUMOylation
Citrullination
ADP-ribosylation
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20
Q

DNA Methylation

A

Methyl groups are added to the DNA molecule (C and A) by METHYL TRANSFERASE enzymes.

  • represses gene transcription when at gene promoter
  • Essential for normal development
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21
Q

What does DNA methylation change without changing the DNA sequence.

A

Methylation changes the activity of the DNA segment

22
Q

What is DNA methylation essential for?

A

Genomic imprinting

  • x-xhromosome inactivation
  • repression of transposable elements
  • aging
  • carcinogenesis
23
Q

What are alterations of DNA methylation an important of

A

cancer development

24
Q

What is hypomethylation associated with

A
  • chromosomal instability

- loss of imprinting

25
Q

What is hypermethylation associated with

A
  • gene promoters

- might be target for epigenetic therapy

26
Q

Which direction does DNA Polymerase synthesize new DNA

A

from 5’ to 3’

27
Q

What does DNA Polymerase need to begin processing

A

a primer with a free 3’ -OH

28
Q

What is DNA Helicase and what does it do?

A

DNA Helicase unwinds DNA

  • it is a protein with 6 identical subunits
  • binds and hydrolyzes ATP
  • Conformational change
  • propels it like a rotary engine
  • passing through a center hole
  • pries apart the helix (1000, BP/sec)
29
Q

Single-Stranded DNA-Binding Protein (SSBP)

A 
Binds Cooperatively to Exposed ssDNA
(Straightens the chain)
-helps stabilize the unwound DNA
-Prevents the formation of hairpins
-DNA bases remain exposed
30
Q

DNA Topoisomerase

A

Relieves overwound supercoils (every 10bp corresponds to one turn)

  • reversible enzyme
  • breaks a phosphodiester bond
  • changes superhelicity
  • relieves supercoiling
  • PHARMA DRUGS THAT TARGET TOPOISOMERASE ARE ANTI CANCER
31
Q

Irinotecan

A

Topoisomerase I inhibitor used to treat colorectal cancer

32
Q

Etoposisde, Anthracylines

A

Topoisomerase II inhibitor

  • etoposide causes secondary leukemias
  • anthracyclines cause cardiotoxicity
33
Q

Why are topoisomerases used as anticancer drugs

A

they block the cell cycle
they generate single and double stranded breaks
they harm the integrity of the genome
they lead to apoptosis and cancer cell death

34
Q

How can UV radiation cause DNA damage

A

UV radiation from sun can produce a covalent linkage between two adjacent pyrimidines (T-T or C-T)
-pyrimidine dimers

35
Q

Spontaneous DNA damage

A

Depurination and deamination

36
Q

Outcomes of spontaneous DNA damage

A
  • DNA replication occurs

- Base deletion or substitution

37
Q

Cross Linking agens

A
  • Nitrogen mustard
  • cisplatin
  • Mitomycin C
  • Carmustine
38
Q

Alkylating Agents

A 
Dimethyl sulfate (DMS)
Methyl methanesulfonate (MMS)
39
Q

Alkylating Agents

A 
Dimethyl sulfate (DMS)
Methyl methanesulfonate (MMS)
40
Q

Intercalacting agents

A

Thalidomide

41
Q

Direct Repair (enzyme repair)

A

Photolyase enzyme repairs pyrimidine dimers

42
Q

Base exclusion repair (BER)

A

single-base mismatches-DNA glycolases

43
Q

Nucleotide excision repair

A

-Xeroderma pigmentosum

44
Q

Mismatch exclusion repair (MER)

A

mismatched base in daughter strand

-Hereditary nonpolyposis colorectal cancers

45
Q

recombination repair

  • nonhomologous end joining
  • homologous recombination
A

double strand breaks, interstrand cross-linking

-BRCA1/2 breast cancer

46
Q

Transcription-coupled repair (TCR)

A

stalled RNA polymerase during transcription (not replication)
-Cockayne syndrome

47
Q

Transcription-coupled repair (TCR)

A

stalled RNA polymerase during transcription (not replication)
-Cockayne syndrome

48
Q

What are the three Post-translational modification (PTM) regulated cellular events

A
  • protein biological activities
  • subcellular ocalization
  • degredation/stability
49
Q

Types of reversible PTMs on proteins

A
  • phosphorylation
  • acetylation
  • ubiquitination
  • SUMOylation
  • methylation
50
Q

What is the start of translation initiating methionine

A

ATG

51
Q

DNA methylation in Humans

A
  • occurs at the 5 position of the pyrimidine ring of the cytosine residues
  • occurs within CpG sites
  • Forms 5-methylcytosines
  • multiple methylated CpG sites in CpG islands of promoters STABLY SILENCES GENES
52
Q

Where is ubiquitin attached to on target cells

A

lysine residues

MCM II (3 decks)

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