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A DNA sequence contains >20 5’GTC trinucleotide repeats. Draw out what happens when six trinucleotide repeats loop out of the newly synthesized strand during DNA replication (replication slippage). Do not draw all repeats, just the six that loop out. Show H-bonds in your drawing for these six trinucleotide repeats. Show (in number of repeats) what results after the subsequent round of DNA replication for the strand with the altered number of repeats. Why are TNR expansions most commonly observed for GC-rich triplet codons?

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Answer:

When six 5’GTC trinucleotide repeats loop out of the newly synthesized strand during DNA replication, 'loop out' structures can form, resulting in an increased number of repeats in the daughter strand. Therefore, after the subsequent round of DNA replication, the strand with the altered number of repeats will have 26 repeats (i.e., 20 repeats + 6 additional repeats due to loop out). The newly synthesized strand containing the additional repeats will then act as a template for the next round of DNA replication, resulting in the expansion of the repetitive sequence.

Triplet repeat expansions are most commonly observed for GC-rich triplet codons because the hydrogen bonding between guanine and cytosine is stronger than that between adenine and thymine. This results in a higher stability of the GC-rich regions, leading to an increased probability of the formation of secondary structures such as hairpins, slipped structures or tetraplexes. These structures can interfere with replication, repair or transcription, leading to the introduction of errors during DNA replication and increasing the likelihood of expansion of the trinucleotide repeat sequences. Therefore, GC-rich regions are more prone to instability and prone to mutations associated with repeat expansions.

Step-by-step explanation:

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