tandem repeat sequence; causes of contraction and/or expansion question

Question

Question:

Which of the following events, occurring within a tandem repeat sequence, will cause an expansion or contraction of the array?

A) Endoduplication B) homologous recombination C) Unequal crossing-over D) Error-prone DNA repair E) Inversion

I know for a fact that upon replication, tandem repeats of DNA (specifically trinucleotide repeats) can form loops which are repaired by mismatch repair enzymes (MSH2-MSH3); and failure to correct this would lead to an expansion of the array post-replication. However, this answer was incorrect.

Could someone assist me with this question? I read up on the topic but its not clear to me why DNA repair defects do not suffice as an answer. I don't also necessarily understand the correct answer (C)

Thanks so much

-Chris

Answer 1

Gene-duplication would not result in contraction (only expansion). Endoduplication would affect all the genes in the chromosome. Error prone repair would cause small-indels but not expansion of the repeats. Inversion will certainly not do anything to the sequence except changing its orientation.

During unequal crossover, the chromosomes can align imperfectly because of multiple alignment sites in the repeat region, thereby leading to unequal crossover products. Crossing over however essentially happens because of homologous recombination. Crossover is a "phenomenon" and not a "mechanism" in a true sense.

Mechanism of crossover

^{Reproduced from: Bugreev, Dmitry V., et al. "The resistance of DMC1 D-loops to dissociation may account for the DMC1 requirement in meiosis." Nature structural & molecular biology 18.1 (2011): 56-60.}

Another thing to note is that homologous recombination in the absence of crossover can lead to expansion of repeats but not contraction (see below).