Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.
PLoS Genet. 2013 Apr;9(4):e1003434. doi: 10.1371/journal.pgen.1003434. Epub 2013 Apr 4.
Although homologous recombination is an important pathway for the repair of double-stranded DNA breaks in mitotically dividing eukaryotic cells, these events can also have negative consequences, such as loss of heterozygosity (LOH) of deleterious mutations. We mapped about 140 spontaneous reciprocal crossovers on the right arm of the yeast chromosome IV using single-nucleotide-polymorphism (SNP) microarrays. Our mapping and subsequent experiments demonstrate that inverted repeats of Ty retrotransposable elements are mitotic recombination hotspots. We found that the mitotic recombination maps on the two homologs were substantially different and were unrelated to meiotic recombination maps. Additionally, about 70% of the DNA lesions that result in LOH are likely generated during G1 of the cell cycle and repaired during S or G2. We also show that different genetic elements are associated with reciprocal crossover conversion tracts depending on the cell cycle timing of the initiating DSB.
虽然同源重组是有丝分裂的真核细胞修复双链 DNA 断裂的重要途径,但这些事件也可能产生负面后果,例如有害突变的杂合性丢失 (LOH)。我们使用单核苷酸多态性 (SNP) 微阵列在酵母染色体 IV 的右臂上定位了大约 140 个自发的相互易位。我们的作图和后续实验表明,Ty 反转录转座元件的反向重复是有丝分裂重组的热点。我们发现,两个同源物上的有丝分裂重组图谱有很大的不同,与减数分裂重组图谱无关。此外,导致 LOH 的约 70%的 DNA 损伤可能是在细胞周期的 G1 期产生的,并在 S 期或 G2 期修复。我们还表明,不同的遗传元件与易位转换区相关,这取决于起始 DSB 的细胞周期时间。