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M2M Unit 1 > DNA Repair > Flashcards

DNA Repair Flashcards

1
Q

Give 3 examples of exogenous causes of mutations in DNA

A

UV
Cosmic radiation
Pollutants

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2
Q

Give 3 examples of endogenous causes of mutations in DNA

A

ROS as byproduct of normal metabolism
Alkylation- addition of methyl group
Hydrolysis

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3
Q

What are two consequences of DNA damage?

A
  1. Block replication or transcription- cell cycle arrest. Cell becomes senescent
  2. Cancer
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4
Q

What happens when there is hydrolysis of the glycosidic bond?

A

Complete loss of base. Called depurination or depyrimidination

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5
Q

Example of a common deamination damage to the base

A

When cytosine is deaminated, it becomes Uracil.

Especially in CpG sites, cytosine is methylated in vivo (5 methylcytosine). Deamination of this methylated cytosine turns it into a thymine.

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6
Q

Example of a common alkylation damage to the base

A

Guanine is frequently methylated (o6-methylguanine). Instead of a GC base pair, you now have an AT base pair

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7
Q

Example of Direct reversal repair

A

Photolyase- fixes TT dimers caused by UV radiation

Methylguanine methyltransferase (MGMT): reverses o6-methylguanine back to guanine)

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8
Q

What type of excision repair is involved in repairing DNA that has not induced a conformational change?

A

Base excision repair (BER)

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9
Q

What enzyme is responsible for excising the glycosidic bond in base excision repair?

A

Glycosylase

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10
Q

After glycosylase excises the glycosidic bond, what site on the DNA is exposed?

A

AP site (apurinic/apyrimidinic site, also known as abasic site)

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11
Q

What type of excision repair is involved in damages that cause conformational changes in the DNA structure?

A

Nucleotide excision repair (NER)

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12
Q

What protein is responsible for recognizing the local bending resulting from UV mediated pyrimidine dimerization?

A

XPC

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13
Q

What are the two ways NER machinery recognizes damage?

A

Global Genome NER

Transcription-Coupled NEr

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14
Q

Where does global genome NER recognize damage?

A

Anywhere in the genome

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15
Q

Where does transcription-coupled NER recognize damage?

A

Within region of active transcription

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16
Q

Defects in global genome NER cause ______.

A

Cancer

e.g. Xeroderma pigmentosum (XP)

17
Q

Defects in transcription-coupled NER result in ______.

A

CNS disorder

e.g. Cockayne syndrome

18
Q

Xeroderma pigmentosum is a result of a defect in which NER mechanism?

A

global genome NER

19
Q

Cockayne syndrome is a result of a defect in which NER mechanism?

A

Transcription coupled NER

20
Q

What protein complex carries out the remaining steps of NER following recognition?

A

TFIIH

21
Q

What proteins within the TFIIH protein complex are involved in the local unwinding of DNA?

A

XPB and XPD

22
Q

What type of repair is involved when the is a mis-incorporation of bases?

A

Mismatch repair

23
Q

What two groups of protein are the main players in mismatch repair?

A

MutS Homolog (MSH): 1,2

MutL Homolog (MLH)/ PMS in Eukaryotes: 1,2, and 6

24
Q

Which class of proteins recognize mispaired nucleotides?

A

MSH (which form dimers)

25
Q

MSH proteins recruit _____.

A

MLH/PMS proteins (which are dimerized)

26
Q

MLH proteins recruit _____.

A

Helicases

27
Q

How do MMR proteins differentiate the newly synthesized strand from the mother strand in e. coli?

A

mother strand is heavily methylated

28
Q

How do MMR proteins differentiate the newly synthesized strand from the mother strand in eukaryotes?

A

Frequent occurrence of nicks is recognized
Easy in lagging stand
Leading strand- marked by transient presence of ribonucleotides

29
Q

Mutations in MMR genes give rise to _______.

A

Hereditary nonpolyposis colorectal cancer (HNPCC), also known as (Taylor) Lynch Syndrome

30
Q

What type of repair occurs when the cell doesn’t have the means to repair?

A

DNA bypass

31
Q

What nucleotide sequence does pol eta add (DNA bypass repair)?

A

AA

32
Q

Briefly describe the steps that occur to repair DNA when there is a lesion in front of the replication fork

A

Translesion repair

PCNA interacts with pol eta and pol iota and moves them towards fork
Pol eta adds AA

Pol iota then extends this new strand

33
Q

Explain DNA damage response

A

Cell recognizes damage and enters cell cycle arrest
ATM and ATR recognize breaks in DNA

Chk1 and Chk 2 initiate repair, arrest, or apoptosis

M2M Unit 1 (9 decks)

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