RECOMBINATION Flashcards

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1
Q

what is homologous recombination important for in genome stability

A

A: Homologous recombination is important for:

  1. Repair of broken replication forks and double-strand breaks (DSBs).
  2. Accurate chromosome segregation during meiosis.
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2
Q

What are the two main roles of meiotic homologous recombination in genetic diversity?

A

A: 1. Creates novel gene combinations.

  1. Crossovers ensure accurate segregation of homologous chromosome pairs in meiosis I.
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3
Q

Q: What are the four types of genetic recombination?

A

A: 1. Homologous recombination (extended homology).

  1. Site-specific recombination (limited homology).
  2. Illegitimate recombination (no homology).
  3. Replicative recombination (transposition, no homology).
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4
Q

homologous recombination

A

highly similar or identical
used for repairing DSB or genetic recombination in meiosis

initiated by DSB, the broken ends are invaded by homologous DNA to use it as a template for repair, often leading to the exchange of genetic info

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5
Q

site specific recombination

A

requires short specific DNA sequences - recognition sites, that are present in both donor and target DNA
enzyme aligns recognition sets and DNA cleaving and rejoining

example - integration of bacteriophage DNA into e.coli or transposable elements

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6
Q

illegitimate recombo

A

no homology , often random and error-prone
NHEJ - non homologous end joining where broken DNA ends are directly ligated together

examples - chromosomal translocations in cancer, lead to genomic instability

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7
Q

transposition - replicative recombo

A

transposable element s- transposons- insert themselves, copy and paste themselves around the genome, no homology needed

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8
Q

What is genetic recombination?

A

A: It is the process of breaking and re-joining DNA strands, often resulting in new DNA sequences, which is essential for creating genetic diversity and evolution.

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9
Q

What happens if there is no recombination in meiosis?

A

Alleles will stay the same, leading to no genetic diversity, and chromosome segregation will occur randomly, possibly leading to errors.

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10
Q

What determines recombination frequency (RF) between genes?

A

A: The physical distance between genes. The closer the genes, the lower the RF, making them more likely to be inherited together.

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11
Q

What is a Holliday Junction (HJ)?

A

: A structure that forms during homologous recombination when DNA strands from two molecules exchange segments.

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12
Q

What is the role of HJ resolvases in homologous recombination?

A

They cleave and resolve Holliday Junctions, either resulting in crossovers (exchanging DNA between homologues) or non-crossovers (original strands stay intact).

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13
Q

What is Rad51 and why is it important in homologous recombination?

A

: Rad51 is a recombinase enzyme that catalyzes the homology search and strand invasion during homologous recombination

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14
Q

Q: What is the function of the BRCA2 protein in homologous recombination?

A

A: BRCA2 promotes the formation of Rad51 filaments on single-stranded DNA (ssDNA). Without sufficient BRCA2, recombination fails, which can lead to genomic instability and cancer

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15
Q

Q: How does site-specific recombination differ from homologous recombination?

A

A: It involves limited homology between DNA sequences and is used for integrating DNA like phage genomes into bacterial chromosomes.

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16
Q

Q: How do crossover events during homologous recombination ensure proper chromosome segregation in meiosis?

A

A: Crossovers hold homologous chromosomes together, allowing them to align properly during meiosis I, ensuring accurate segregation.

17
Q

Q: What is the role of the protein cohesin in meiosis?

A

A: Cohesin holds sister chromatids together, and separase cleaves cohesin to allow chromatid separation during anaphase.

18
Q

Q: How do double Holliday junctions (double HJ) increase genetic diversity?

A

A: Double HJs can be resolved in four different ways, two of which result in crossover events that generate recombinant chromosomes, contributing to genetic diversity.

19
Q

Q: What is illegitimate recombination and give an example of where it occurs?

A

A: Illegitimate recombination occurs without homology, such as when the HIV virus integrates into the host genome randomly.

20
Q

what are the causes of replication fork pausing

A

A: Replication forks pause due to:

RNA blocking the way.

DNA secondary structures.

Tightly bound proteins.

Heterochromatin unwinding.

Telomeres.

21
Q

What can cause replication forks to become unstable?

A

: Damage to DNA, such as damaged nucleotides or crosslinked nucleotides, can cause replication forks to pause and become unstable

22
Q

What are stalled replication forks (RF)?

A

Stalled replication forks are those that cannot pass through a replication barrier due to DNA damage or other obstacles.

23
Q

What happens when a replication fork stalls?

A

A stalled replication fork can lead to a single-stranded DNA break (ssDNA), which is then processed as a double-stranded break (DSB). Rad51 filaments form on the resected 3’ end to allow homologous repair.

24
Q

How is the replication fork re-established after a break?

A

The broken end invades the unbroken sister chromatid, and the replication fork is re-established. The two sister chromatids are connected by a nicked Holliday junction, which is resolved by Holliday junction resolvase.

25
Q

What is bacterial conjugation and how does it affect the cell?

A

Bacterial conjugation is the transfer of genetic material through a fertility plasmid, changing the sex of the cell (the recipient becomes a donor with the fertility plasmid).

26
Q

How can plasmids integrate into bacterial chromosomes during conjugation?

A

If the plasmid integrates into the donor’s chromosome, the donor’s chromosome can be transferred along with the plasmid to the recipient, allowing recombination between donor and recipient chromosomes.

27
Q

Why are circular chromosomes incompatible with meiotic recombination?

A

Circular chromosomes would need an even number of crossovers to properly segregate, which is why linear chromosomes are used in eukaryotic meiosis.

28
Q

What is the role of recombination in genome maintenance?

A

A: Recombination maintains genome integrity by:
1 .Repairing broken replication forks.

  1. Ensuring genome stability via homologous recombination.
  2. Contributing to genetic diversity in meiosis.
  3. Allowing proper segregation of linear chromosomes in meiosis.
  4. Stabilizing linear chromosomes through telomeres.

6.Suppressing cancer by downregulating telomerase in large animals and humans.

29
Q

What is the significance of homologous recombination in cells?

A

Cells have evolved homologous recombination as a key mechanism to repair broken replication forks, ensuring the stability of the genome.

30
Q

What is the importance of HR recombinases across species?

A

HR recombinases, such as Rad51 in humans, are conserved from bacteria to humans, emphasizing their fundamental role in homologous recombination and genome stability.

31
Q

site specific vs illegitimate

A

site specific requires enzymes whilst illegitimate does not

32
Q

site specific examples

A

integration and Excision of Phage DNA

Integration of Retroviral DNA
Example: HIV uses integrase to insert its DNA into the host genome at specific sequence contexts.

Mating-Type Switching in Yeast

33
Q

illegitimate examples

A

Random Integration of Transgenes

Non-Homologous End Joining (NHEJ)

Chromosomal Translocations

Double-Strand Break-Induced Mutations

Retrotransposon Insertion

34
Q

how to determine between site specific and illegitimate

A

Is there a specific sequence recognized (e.g., att, LoxP)?
Yes → Site-specific recombination.
No → Continue.

Is a recombinase or integrase enzyme involved?
Yes → Site-specific recombination.
No → Continue.

Does it serve a biological role (e.g., viral integration, antibody diversity)?
Yes → Site-specific recombination.
No → Illegitimate recombination.