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draco7 draco7
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10 years ago
Trying to work out and reason through this practice question to help me on my test.

"Briefly explain why non-homologous end joining is overwhelming favored over homologous recombination repair for fixing double strand DNA breaks in mammalian cells in G1. Why is this bias reversed during G2?"

So I reckon that non-homologous end joining is favored in G1 because although original base pairing is lost and chewed back by exonuclease before the DNA is re-ligated, the loss of base pairs isn't critical due to the imminent S phase, which will ensure the DNA is further re-synthesized, thus mitigating the effect of lost base pairs.
However, for G2 nonhomologous recomb. is favored because in this method base pairs are re-added before getting re-ligated, ensuring no bases are lost. This is critical because the next phase is mitosis, and all of the DNA must be synthesized to this point; any loss of DNA before mitosis would probably lead to mutations when the cell eventually divides.

Is my reasoning accurate? Do holiday junctions add to the explanation or does this suffice? Please chime in and discuss!
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wrote...
Staff Member
10 years ago
This is the first time reading about this, and I'm a biologist by trade Face with Stuck-out Tongue

One source states:

NHEJ removes DSB genome by simply joining the DNA ends without homology rec and without ensuring sequence restoration around the break.

(link)

Another source states:

Chromosome breaks, often with damaged or missing DNA flanking the break site, are an important threat to genome stability. They are repaired in vertebrates primarily by nonhomologous end joining (NHEJ). NHEJ is unique among the major DNA repair pathways in that a continuous template cannot be used by DNA polymerases to instruct replacement of damaged or lost DNA. Nevertheless, at least 3 out of the 17 mammalian DNA polymerases are specifically employed by NHEJ. Biochemical and structural studies are further revealing how each of the polymerases employed by NHEJ possesses distinct and sophisticated means to overcome the barriers this pathway presents to polymerase activity. Still unclear, though, is how the resulting network of overlapping and nonoverlapping polymerase activities contributes to repair in cells.

(see link below)

Hope this helps your understanding.
Source  http://www.ncbi.nlm.nih.gov/pubmed/22987211
- Master of Science in Biology
- Bachelor of Science
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