PMC

Fig. 1. Tandem repeat rearrangement by unequal crossover between sister chromatids. Reciprocal exchange leads to simultaneous contraction of one of the repeats and expansion of the other.

Fig. 3. Experimental system used to study tandem repeat instability during mitotic gene conversion induced by an endonuclease in yeast. After induction of a DSB on a yeast chromosome by an inducible endonuclease, yeast cells can repair the broken molecule using a tandem repeat-containing homologous donor sequence. During DNA synthesis associated with DSB-repair, slippage of the newly synthesized strand(s) may occur, giving rise to contractions or expansions of the tandem repeat in the recipient molecule. The blue circle represents the chromosome centromere.

Fig. 2. Recombination models. In all models, gene conversion is initiated by a DSB, and strand invasion of the homologous template is initiated by a resected 3′ end. Arrows represent DNA synthesis associated with DSB-repair. The broken molecule (‘donor’) is shown in blue, the template molecule (‘recipient’) is shown in red, newly synthesized DNA is shown in orange. Tandem repeats are represented by hatched lines. (A) model. Resolution of the two four-stranded structures called ‘Holliday junctions’ (circled in black) results in gene conversion associated with crossovers in 50% of the cases. (B) SDSA model. Resolution is achieved by unwinding the two newly synthesized strands from the template and annealing them. No crossover is expected. (C) SDSA model of tandem repeat rearrangements. The newly synthesized strands both contain repeats and their out-of-frame annealing can lead to contraction or expansion of the tandem repeat. (C′) Alternatively, contraction and expansion can result from unwinding and out-of-frame re-invasion of one (or both) the newly synthesized strand(s). Only one kind of event (expansion) is shown here. Several rounds of unwinding/re-invasion could take place during a single gene conversion, leading to successive rounds of DNA synthesis.