genomic functions Flashcards

1
Q

What is the base excision repair mechanism?

A

For single base mismatches that don’t distort (DNA polymerase does this)
DNA glycosylase detects and removes the mismatched base.
AP endonuclease cuts the phosphodiester bond
AP lyase removes the deoxyribose phosphate
DNA polymerase Beta replaces the nucleotide
DNA ligase seals the nick

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the mechanism for nucleotide excision repair? (often chemically induced damage like thiamine dimers)

A

NER complex recognizes distortions and nicks DNA on both sides of the distorting adduct.
DNA polymerase then fills the gap
DNA ligase seals the nick

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe transcription-coupled repair

A

When RNA polymerase is stalled at lesions in DNA it directs repair machinery to it.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe Mismatch repair

A

MER complex binds to DNA, recognizes mismatch in daughter strand, then cuts the segment
DNA polymerase and ligase fill and seal the gap.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How is DNA packaged and unwound by histones?

A

Lys and Arg are positive (1/5 of histone), DNA negative charge
Histone acetylation: loosely packed for transcription by removing positive charge
Histone methylation: loosely packed for transcription by physical interference

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

describe how histones are modified

A

HIstones have tails upon which various enzymes work.
Writer enzymes add modifications
Eraser enzymes remove them
Reader enzymes bind to the modification to further alter gene activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Helicase

A

unwinds DNA helix

ATP fuels it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Topoisomerase

A

Relieves over-wound supercoils;

reversible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

DNA polymerase a

A

In complex with primase.

Synthesizes RNA-DNA primer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

DNA polymerase d and e

A

Synthesize new DNA chain in the 5to3 direction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Flap endonuclease 1

A

REmoves RNA primers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

DNA polymerase d

A

Fills in gaps

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

DNA ligase

A

seals nicks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What enzyme is inhibited during DNA replication?

A

Topoisomerase is inhibited by
Etoposide in eukaryotes
Flouroquinolones in prokaryotes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the relationship between telomeres and telomerase?

A

telomeres are the primers for replication. When the primer runs out then the cell cannot replicate more DNA
Telomerase restores the lost primer each division. It has a RNA template for reverse transcription. One step that cancer must accomplish is further activation of telomerase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What causes pyrimidine dimers?

A

UV radiation causes adjacent pyrimidines to form covalent bonds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the problem involving methylated cytosines?

A

If C is methylated then it often spontaneously is converted to T. In CpG islands there is a high frequency of methyl-C. This methylation silences Cancer/DNA repair genes. If converted to T often in the island then silencing is ineffective.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Name some cross linking agents

A

Nitrogen mustard, Cisplatin, Mitomycin C, Carmustine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Name some alkylating agents:

A
Dimethyl sulfate (DMS)
Methyl mehanesulfonate (MMS)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Name some Intercalating agents.

A

Ethidium bromide
Thalidomide
Doxorubicin
Daunomycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Direct repair

A

pyrimidine dimer repair and methylguanine repair
DNA photolyase
Methylguanine methyltransferase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Base excision repair enzymes

A

DNA glycolases, AP endonuclease, AP lyase, DNA polymerase, DNA ligase

23
Q

Nucleotide excision repair enzymes

A

NER protein complex, DNA polymerase, DNA ligase

24
Q

Mismatch excision repair enzymes

A

MER complex, helicase/endonuclease, DNA polymerase, DNA ligase

25
Q

Recombination repair enzymes

A

BRCA1/2

a bunch of enzymes

26
Q

Transcription-coupled repair enzymes

A

depends on the cause of the lesion in the DNA

27
Q

Translesion synthesis enzymes

A

DNA polymerases;

repairs thymine dimers or apurini AP sites

28
Q

Describe Xeroderma pigmentosum

A

Mutation in the NER complex makes it so UV damage cannot be fixed. Pts easily sunburn, have dry and scaly skin, prone to develop squamous cell carcinomas

29
Q

describe hereditary nonpolyposis

A

Mutation to one of the alleles in the MER complex have and increased susceptibility to hereditary nonpolyposis colorectal cancers.
A mutation to the remaining allele would render MER nonfunctional=tumor

30
Q

describe cockayne syndrome

A

Mutation of genes involved in TCR of DNA repair.

31
Q

describe BRCA

A

Mutation in tumor suppressor genes involved with treatment.

32
Q

Describe alternative splicing

A

Alternative splicing, or differential splicing, is a regulated process during gene expression that results in a single gene coding for multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final, processed messenger RNA

33
Q

snRNA

A

small nuclear RNA part of splicosomes (splicing)

34
Q

scRNA

A

involved in protein synth and transport,

associated with SRP (ER and making transmembrane proteins)

35
Q

RNaseP

A

catalytic RNA involved in cleavage and removal of extra RNA sequences of tRNAs

36
Q

siRNA

A

short, derived from transposons, complementary to mRNA, inhibit translation of mRNA and enhance their degradation in RNA-induced silencing complexes (RISCs)

37
Q

miRNA

A

like siRNA, short, involved in posttranscriptional regulation of gene expression

38
Q

describe transposons

A

A transposable element (TE or transposon) is a DNA sequence that can change its position within a genome, sometimes creating or reversing mutations and altering the cell’s genetic identity and genome size.

39
Q

Describe LTR retrotransposons

A

RNA is transcribed, then it is reverse transcribed into new DNA, then that DNA is inserted at another location on the DNA

40
Q

Describe non-LTR retrotransposons

A

RNA is transcribed, then it is reverse transcribed directly into the genome.

41
Q

Heterochromatin vs euchromatin

A

hetero-packed, less active;

eu; unpacked, more active

42
Q

heterochromatin features

A

stains darkly, highly concentrated at centromeres and telomeres,

43
Q

What residues on the histone complex interact with DNA?

A

Lysine and Arginine (1/5 of histone compilation; positive charge)

44
Q

Histones are conserved?

A

histones are highly conserved, any mutation would likely be lethal

45
Q

Describe HDAC

A

histone de-acetylase i think. These close the chromatin.
Inhibited by vorinostat, entinostat;
counteracts p53 by not allowing the trans factor to create p21

46
Q

Which direction does DNA polymerase synthesize new DNA?

A

5’ to 3’;

it synthesizes in a bi-directional manner

47
Q

describe cross linking and intercalating

A

intercalating is a positioning of an agent covalently between the base pairs
cross linking just links them?

48
Q

Xeroderma pigmentosum is correlated with a defect in which repair mechanism?

A

Nucleotide excision repair NER

49
Q

Hereditary nonpolyposis non-colorectal cancer is associated with a defect in which DNA repair mechanism

A

MER mismatch excision repair

50
Q

BRCA1/2 breast cancers are associated with a defect in which DNA repair mechanism?

A

Recombinant repair

51
Q

Cockayne syndrome is associated with a defect in which repair mechanism?

A

TCR transcription-coupled repair

52
Q

Describe DNA glycosylases

A

at least six different types
each recognizes a specific type of altered base and catalyzes it’s removal
after base is removed then nuclease, lyase, polymerase, then ligase complete removal and replacement

53
Q

DNA polymerase have with repair mechanisms attached to it?

A

DNA glycosylase and mismatch repair functions