Module 02 - Section 04 Flashcards

DNA Repair

1
Q

What is a karyotype

A

Visualization of the number and appearance of the chromosome within a cell, where each chromosome pair is labelled with a different colour

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2
Q

What is recombination?

A

Rearrangement of genetic material, especially by crossing over in chromosomes

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3
Q

What are two prime examples of problems that occur within a cancer cell?

A

(1) Aneuploidy

(2) Chromosomal translocation

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4
Q

What is aneuploidy?

A

Presence of an abnormal number of chromosomes in a cell

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5
Q

What causes aneuploidy? (2)

A

Mitotic segregation defects or chromosomal non-disjunction.

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6
Q

What is chromosomal non-disjunction?

A

Failure of one or more pairs of homologous chromosomes or sister chromatids to separate nomrally during and after mitosis

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7
Q

What is chromosomal translocations?

A

Abnormality caused by rearrangement of parts between non-homologous (not part of the same pair)
- can be direct swtiching of material between 2 chromosomes of large scale deletions/insertions

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8
Q

What generally causes chromosomal translocations?

A

Errors during homologous recombination or double strand break repair

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9
Q

What is a DSB?

A

Double-strand break is a break in the phosphodiester backbone on both strands of DNA at the same site

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10
Q

When and why do DSBs occur?

A

(1) During replication, when replication fork encounters a single-strand break in the template strand, which then become a DSB because DNA breaks make it impossible for DNA replication to continue
(2) Exposure to UV or gamma radiation - result goes beyond a simple mutation that may or may not affect cellular function, typically lead to cell death

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11
Q

Which bacteria can withstand tremendous amounts of radiation because of its DNA regeneration?

A

Deinococcus Radiodurans

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12
Q

How does deinoccocus radiodurans deal with radiation?

A

It contains many copies of its DNA to ensure there is always a back up template for repair. After radiation, overlapping DNA fragments are spliced together and the entire genome is reconstituted accurately within a few hours.

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13
Q

What is inherent to every free-living organism?

A

Capacity for the enzymatic repair of DSBs

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14
Q

What is recombinational DNA repair?

A

Group of recombination processes directed at the repair of DNA strand breaks or cross links, especially at inactivated replication forks.

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15
Q

What does recombinational DNA repair require?

A

Another undamaged, homologous, double stranded DNA – either the second copy of the chromosome or the sister chromatid

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16
Q

Describe the mechanism of action of recombinational DNA Repair

A

(1) Helicases and nucleases selectively degrade the 5’ ending and create 3’ overhangs at the site of the break - ssDNA is coated and protected single-strand binding proteins (SSBs)
(2) Recombinases catalyze 3’ ssDNA extensions invading the homologous chromosome after replacing SSBs - Invading strand displaces one strand of intact homologous chromosome and base pairs with the other (D-Loop)
(3) 2nd strand invasion takes place, similar to the first, producing 2 DNA cross over points
(4) Replicative extension of the invading strand by Pol III, as the 3’ ends of the invading strand can act as primers for DNA Synthesis
(5) 2 possible pathways to complete:
A: Synthesis-dependent strand annealing (SDSA); lengthened invading DNA strand can simply be displaced and annealed to each other
B: Double-Strand Break Repair (DSBR): ligating the strands while they are still linked at the holliday intermediate by Holliday junction resolvases

17
Q

What is D Loop

A

Structure created by strand invasion by the 3’ single-stranded extension

18
Q

What are recombinases?

A

Restricion endonucleases and DNA ligases combined into a single efficient package

19
Q

What are Holliday intermediates?

A

The four branched crossover junction with all DNA strands intact such that each branch is a segment of duplex DNA

20
Q

What are Holliday junction resolvases

A

Specialized endonucleases that recognize and cleave the Holliday intermediates

21
Q

What are the 2 ways Holiday intermediates can be cleaved?

A

Both at the X site or both at Y sites = non crossover, cleavage sites will be exchanged but chromosomes will not
One at X site one at Y site = crossover, genetic material outside of repair site are from 2 separate chromosomes

22
Q

Which DNA polymerases is involved in bacterial recombinational DNA repair?

A

Pol I

23
Q

What are the most deleterious DNA lesions?

A

Double-Strand Breaks