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ML2001: Introductory Molecular Biology > DNA Repair > Flashcards

DNA Repair Flashcards

1
Q

What are Mutations?

A

Permanent change in DNA sequence

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2
Q

What types of mutations are essential for evolution?

A

Silent & Non-Silent mutations

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3
Q

How can DNA become damaged?

A
  • Radiation
  • Mutagens
  • Replication errors
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4
Q

How many proteins does the human genome encode for dedicated to DNA repair?

A

More than 130

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5
Q

What are FOUR mechanisms for DNA repair in cells?

A
  1. Mismatch Repair
  2. Base-Excision Repair
  3. Nucleotide-Excision Repair
  4. Direct Repair
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6
Q

Who is recognised for their work in Mismatch DNA Repair?

A

Paul Modrich

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7
Q

What does Mismatch DNA Repair do?

A

Fixes replication errors & improves accurary 100-1000 fold

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8
Q

What is Mismatch DNA Repair based on?

A

Distinguishing old and new strands

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9
Q

How does Mismatch DNA Repair work in E. coli?

A

Methylation on Adenine within GATC

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10
Q

What are the steps in Mismatch DNA Repair?

A
  1. Mut S complex binds to mismatched base pair
  2. Mut L binds to Mut S
  3. Mut L / Mut S complex moves along DNA until it finds a Mut H bound at hemimethylated GATC sequence
  4. Mut H is an endonuclease that cleaves unmethylated strand

This triggers repair

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11
Q

Mutations in which proteins causes colon cancer?

A

MutS & MutL
(MSH Proteins)

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12
Q

Who is known for their work in Base Excision Repair?

A

Tomas Lindahl

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13
Q

Which enzymes recognise lesions in DNA?

A

DNA Glycosylases

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14
Q

What are the steps in Base Excision Repair?

A
  1. Generates apurinic or apyrimidinic (AP) site
  2. AP site cut by endonuclease
  3. Segment of DNA is replaced by DNA Pol I using its 5’-3’ endonuclease activity
  4. Ligation of DNA strands (DNA Ligase)
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15
Q

Who is known for their work with Nucleotide Excision Repair?

A

Aziz Sancar

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16
Q

What are Nucleotide Excision Repair needed for?

A

Lesions that distort helix

  • UV: pyrimidine dimers
  • Cigarette smoke: benzo-pyrene guanine
17
Q

What enzyme complex does Nucleotide Excision Repair use?

A

Multi-subunit enzyme complex: Exinuclease

18
Q

How does Exinuclease work?

A

Hydrolyses phosphodiester bonds on either side of distortion

19
Q

What is Xeroderma Pigmentosum (XP)?

A

Inherited condition where nucleotide excision repair is inactive

  • Sunlight sensitivity (pyrimidine dimers)
  • Susceptible to melanoma
20
Q

When is Direct Repair used for DNA repair?

A

When there is no removal of bases or nucleotides

21
Q

Where does Direct Repair occur?

A

In bacteria and yeast

22
Q

What causes Direct Repair?

A

Damage by alkylating agents

23
Q

What is the impact of DNA damage encountered during DNA replication?

A
  • Unrepaired lesion encountered; replication stalled
  • Replication fork may collapse
  • Other repair pathways engaged
24
Q

How is Homologous Recombination repair mediated?

A
  • BRCA2 and the RAD51 recombinase
  • Requires another DNA strand
25
Q

How is Non-Homologous End Joining (NHEJ) mediated?

A
  • DNA-dependent protein kinase and DNA ligase IV complex
  • Modify and re-join DNA ends

Error Prone

26
Q

Dysfunction in which DNA repair mechanism causes susceptibility to skin cancer?

A

Inactive nucleotide excision repair

27
Q

Dysfunction in which genes cause breast cancer?

A

BRCA1 and BRCA2

DNA repair of double stranded breaks

28
Q

Mutation or inactivation of which tumour suppressor protein is a marker in many cancers?

A

p53

29
Q

Mutation or inactivation of which tumour suppressor protein is a marker in many cancers?

A

p53

30
Q

How is Poly-ADP Ribose Polymerase used in DNA repair and cancer therapy?

A
  • Crucial for detecting DNA strand breaks and other DNA damage in human cells
  • Synthesises poly ADP ribose polymer at site
  • Signal for recruitment of repair machinery

ML2001: Introductory Molecular Biology (18 decks)

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