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MCM Exam II > Function And Dysfunction In Genomic Regulation > Flashcards

Function And Dysfunction In Genomic Regulation Flashcards

1
Q

How much volume of the cell does the nucleus take up?

A

6%

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2
Q

Purines

A

Adenine and guanine

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3
Q

Pyrimidines

A

Thiamine, cysteine, and uracil

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4
Q

What linkages are between DNA and the his tone octamer?

A

142 hydrogen bonds. Helps with hydrophobic interactions and salt linkages

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5
Q

What makes up 20% of histone protein amino acid residues?

A

Lysine and arginine. Makes it to where there are a lot of positive charges that will be attracted to the negative DNA backbone

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6
Q

Nucleosomes

A

Basic unit of chromosome packing. Made up of 8 histone proteins

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7
Q

Chromatin

A

Histone proteins and DNA

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8
Q

Euchromatin

A

Lightly packed chromatin. Typically under active transcription and is the most active portion of the genome. Around 92% of genome

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9
Q

Heterochromatin

A

Tightly bound DNA and his tones. Will stain dark in all phases. Concentrated at centromeres and telomeres.

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10
Q

How many chromosomes are in the human genome?

A

46

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11
Q

CGH

A

Comparative genome hybridization helps find copy number variances. Use CHIP with DNA from one person and with DNA from a reference DNA. Helps detect deletions of genes

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12
Q

RNAi

A

A process where RNA molecules (miRNA) will inhibits gene expression or translation. This neutralizes the targeted mRNA molecules

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13
Q

LTRs

A

Identical sequences of DNA that repeat hundreds to thousands of times. Found at either end of retrotransposons and are formed by rever transcription of retro viral RNA
Insert genetic material into host genomes

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14
Q

What do introns begin and end with?

A

GT and AG

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15
Q

Histone deacetylation

A

Represses gene expression as the histone are would too tightly around the DNA

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16
Q

Histone acetylation

A

Acetylations in the chromatin allow for space between the histones so there is more room and they will be transcriptionally active

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17
Q

What area of histones are targeted for PTM?

A

Histone tails, especially on H3 and H4. The core can also be modified

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18
Q

DNA methylation

A

Represses gene transcription when at the gene promoter
Associated with genomic imprinting, x-chromosome inactivation, repression of transposable elements, aging, and carcinogensis

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19
Q

CpG islands

A

At the gene promoter. Will typically be hypermetyhlated and cause transcriptional silencing. Can be inherited by daughter cells.

20
Q

Hypomethylation

A

Causes chromosomal instability and a loss of imprinting

21
Q

Hypermethylation

A

Located by gene promoters; can arise secondary to gene (oncogene suppressor) silencing.

Could be a target for epigenetic therapy

22
Q

Which direction is DNA synthesized?

A

5’ to 3’ by DNA polymerase

23
Q

What three things are required for DNA replication?

A

Separation of the two parental strands
dATP, dGTP, dCTP, dTTP
A primer with a free 3’ OH

24
Q

Semi-discontinuous replication

A

Replication of the leading strand is continuous, while the Okazaki fragments will have discontinuous synthesis of lagging strand

25
Q

DNA helicase

A

Unwinds the DNA.
Binds by hydrolyzing ATP then undergoes a conformational change and passing along. It passes the leading strand through the center hole and pries the helix apart at 1000 BP/sec

26
Q

SSBP

A

Single stranded DNA-Binding protein that will bind to exposed DNA and prevent degradation.

W/O, hairpins will form and DNA polymerase can’t complete its job

27
Q

Topoisomerase

A

Relives overwound supercoils.

A reversible enzyme that will break a phosphodiesterase bond and relive supercoiling

Drugs that target this enzyme are anti-cancer drugs

28
Q

Topoisomerase I inhibitor

A

Irinotecan

Used in colorectal cancer and the FOLFORI regimen

29
Q

Topoisomerase II inhibitor

A

Etoposide. Causes secondary leukemias

Anthracyclines cause cardiotoxicity

30
Q

UV radiation

A

Produces pyrimidine diners - covalent linkage between two adjacent pyrimidines (T-T or C-T)

31
Q

Ionizing radiation

A

Causes strand breaks, modification of bases, and DNA/protein cross links (like a thymine tyrosine cross link)

32
Q

Depurination

A

Spontaneous DNA damage. Lose about 5000 purines/day

33
Q

Deamination

A

Spontaneous C to U change happens about 100 bases per day

34
Q

Methylated cytosine in CpG islands

A

Associated with inactive genes; delaminates of methyl-c can cause mismatched T and G.

Methylation of these islands silence genes

DNA glycosylase will recognize and remove the T but repair is typically ineffective

35
Q

BPDE

A

A carcinogen that can be formed from benzo(a)pyrene via metabolism

36
Q

Cross linking agents that can cause DNA damage

A

Nitrogen mustard, cisplatin, mitomycin C, carmustine

37
Q

Alkylating agents

A

Dimethyl sulfate (DMS) and methyl methanesulfonate

38
Q

Intercalating agents that cause DNA damage

A

Ethidium bromide, thalidomide, doxorubicin, and daunomycin

39
Q

Direct repair fixes what damage?

A

Pyrimidine diners or O6-methylguanine.

40
Q

Base Excision repair fixes what damage

A

Single base mismatches, nondistoring alterations like depurination

41
Q

Nucleotide excision repair fixes what type of damage

A

Chemical adducts that distort DNA

Damage can lead to xeroderma pigmentosum

42
Q

Mismatch excision repair fixes what kind of damage?

A

Mismatched bases in the daughter strand. Errors can cause hereditary nonpolposis and colorectal cancers

43
Q

Recombination repair: NHEJ and HR

A

Fixes double strand breaks and inter strand cross linking. Can cause BRCA1/2 breast cancer

44
Q

Transcription coupled repair (TCR) fixes

A

Stalled RNA polymerase during transcription. Dysfunction can cause cockayne syndrome

45
Q

Ataxia telangiectasia

A

Leukemia, lymphoma, genominstability. The process affected in the ATM protein - a protein kinase activated by double strand breaks

46
Q

BRCA2

A

Breast, ovarian, and prostate cancer. Affects repair by homologous recombination

47
Q

Fanconi anemia groups A-G

A

Causes congenital abnormalities, leukemia, and genome instability. Affects DNA interstrand cross-link repair

MCM Exam II (9 decks)

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