Lecture 10 Flashcards

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0
Q

What are 5 causes of double strand breaks?

A

Ionizing radiation, Alkylating agents, reactive oxygen species, torsional stress, and some enzymes

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1
Q

What is the most severe form of DNA damage?

A

Double strand breaks (DSBs)

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2
Q

What is an example of an Alkylating agent that can cause DSBs?

A

Cisplatin

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3
Q

What are the two types of double strand break repair?

A

Non-homologous end-joining (NHEJ) and homologous recombination (HR)

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4
Q

How does NHEJ work?

A

Broken ends are simply lighted back together

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5
Q

How does homologous repair work?

A

Any missing DNA bases are copied from homologous chromosome and the ends are lighted together

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6
Q

Which subpathway is the main repair pathway for DSBs generated by ionizing radiation?

A

NHEJ

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7
Q

When is HR most active?

A

During DNA replication

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8
Q

When is NHEJ most active?

A

G1/G0 phases of cell cycle

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9
Q

What is a Holiday Junction?

A

Junction between four strands of DNA

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10
Q

Where are Holliday Junctions found?

A

During homologous repair

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11
Q

During HR, what proteins bind the ends of the breaks and seek out the homologous chromosome?

A

RAD51 and BRCA-2

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12
Q

What are the three steps of homologous recombination?

A

Strand invasion, branch migration, and Holliday Junction

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14
Q

Ligation of ends during HR is accomplished by what enzyme?

A

DNA ligase 1

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15
Q

What is BRCA1’s role in homologous recombination?

A

Activates checkpoint

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16
Q

What complex is responsible for recognizing and binding DNA ends during NHEJ?

A

Ku70+Ku80

17
Q

What are the three steps of eukaryotic mismatch repair?

A
  1. Recognition 2. Excision 3. Resynthesis
18
Q

What protein complex is responsible for recognizing and binding mismatched bases?

A

MSH2:MSH6 complex (MutS)

19
Q

What activities are present during excision?

A

Unwinding via helical and removal of base pairs via exonuclease

20
Q

What protein fills the gap left by the DNA?

A

DNA polymerase D

21
Q

What causes Lynch Syndrome?

A

Loss of function if MMR genes

22
Q

What cancers are Lynch Syndrome associated with?

A

Colorectal cancers and endometrial cancers

23
Q

What is a strong indicator of damaged/impaired mismatch repair function?

A

Microsatellite instability

24
Q

What mutations does X-ray exposure cause?

A

Oxidized bases, ssDNA breaks, double strand breaks

25
Q

What is PARP1 responsible for?

A

Single strand break repairs

26
Q

What is BRCA2’s role in homologous recombination?

A

Stimulates recombination