David H. Koch Institute for Integrative Cancer Research and Howard Hughes Medical Institute (HHMI), Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science. 2011 Aug 19;333(6045):1026-30. doi: 10.1126/science.1206412.
Aneuploidy decreases cellular fitness, yet it is also associated with cancer, a disease of enhanced proliferative capacity. To investigate one mechanism by which aneuploidy could contribute to tumorigenesis, we examined the effects of aneuploidy on genomic stability. We analyzed 13 budding yeast strains that carry extra copies of single chromosomes and found that all aneuploid strains exhibited one or more forms of genomic instability. Most strains displayed increased chromosome loss and mitotic recombination, as well as defective DNA damage repair. Aneuploid fission yeast strains also exhibited defects in mitotic recombination. Aneuploidy-induced genomic instability could facilitate the development of genetic alterations that drive malignant growth in cancer.
非整倍体降低细胞适应性，但它也与癌症有关，癌症是一种增殖能力增强的疾病。为了研究非整倍体导致肿瘤发生的一种机制，我们研究了非整倍体对基因组稳定性的影响。我们分析了携带单个染色体额外拷贝的 13 株酿酒酵母菌株，发现所有非整倍体菌株都表现出一种或多种形式的基因组不稳定。大多数菌株显示出增加的染色体丢失和有丝分裂重组，以及 DNA 损伤修复缺陷。非整倍体裂殖酵母菌株也表现出有丝分裂重组缺陷。非整倍体诱导的基因组不稳定性可能有助于促进遗传改变的发展，从而推动癌症的恶性生长。
