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Review
. 2021 Jan 14;22(2):786.
doi: 10.3390/ijms22020786.

Origin, Regulation, and Fitness Effect of Chromosomal Rearrangements in the Yeast Saccharomyces cerevisiae

Xing-Xing Tang  1 , Xue-Ping Wen  1 , Lei Qi  1   2 , Yang Sui  1   2 , Ying-Xuan Zhu  1 , Dao-Qiong Zheng  1
Affiliations
Review

Origin, Regulation, and Fitness Effect of Chromosomal Rearrangements in the Yeast Saccharomyces cerevisiae

Xing-Xing Tang et al. Int J Mol Sci. .

Abstract

Chromosomal rearrangements comprise unbalanced structural variations resulting in gain or loss of DNA copy numbers, as well as balanced events including translocation and inversion that are copy number neutral, both of which contribute to phenotypic evolution in organisms. The exquisite genetic assay and gene editing tools available for the model organism Saccharomyces cerevisiae facilitate deep exploration of the mechanisms underlying chromosomal rearrangements. We discuss here the pathways and influential factors of chromosomal rearrangements in S. cerevisiae. Several methods have been developed to generate on-demand chromosomal rearrangements and map the breakpoints of rearrangement events. Finally, we highlight the contributions of chromosomal rearrangements to drive phenotypic evolution in various S. cerevisiae strains. Given the evolutionary conservation of DNA replication and recombination in organisms, the knowledge gathered in the small genome of yeast can be extended to the genomes of higher eukaryotes.

Keywords: DNA repair; S. cerevisiae; chromosomal rearrangement; recombination; whole-genome sequencing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
DSB end resection and repair pathway. After DSB formation, Ku binds to the DSBs and promotes the classic NHEJ pathway. NHEJ generally cause small deletions. The MRX-Sae2 complex initiates the resection and Exo1 extends the resection to expose longer 3′ ssDNA that is bound by RPA to prevent degradation. MMEJ and SSA are two alternative end-joining pathways, both of them can result in deletion or translocation. In the homologous recombination pathway, the 3′ ssDNA is coated with Rad51 and invades the homologous template to form a D-Loop. DNA synthesis is represented by an arrow and newly synthesized DNA by a broken line. Homologous recombination leads to multiple outcomes (non-crossover, crossover, gene conversion, and translocation) depending on what templates were used and in which way the D-Loop was processed. Abbreviations: NHEJ, Nonhomologous end joining; MRX, Mre11-Rad50-Xrs2 complex; RPA, replication protein A; MMEJ, microhomology-mediated end joining; SSA, single strand annealing; SDSA, synthesis-dependent strand annealing; DSBR, double-strand break repair; BIR, break-induced replication; MIR, multi-invasion-induced rearrangement.
Figure 2
Figure 2
Two methods to generate on-demand chromosomal rearrangements. (A) Generation of targeted translocation with CRISPR-Cas9. Using two different gRNAs, two DSBs are simultaneously generated on different chromosomes by Cas9. DSBs are then repaired in trans with a chimerical donor DNA oligonucleotide, resulting in designed translocation. (B) PCR-mediated construction of a segmentally duplicated chromosome. The most left/right regions (400 bp; white rectangle) of a target region were amplified by PCR. The primers A, B, C, and D varied with the target site. A DNA fragment containing a centromere (CEN4) and the selective marker 1 cassette, paired with the PCR product that was produced by primers A and B, were used to generate “duplicate DNA module 1” by overlap extension PCR. Similarly, a DNA fragment containing the selective marker 2 and the PCR product produced by primers C and D were used to amplify “duplicate DNA module 2”. Duplicate DNA modules were then introduced into yeast cells to duplicate the selected region by homologous recombination and DNA replication.
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