Chen C, Umezu K, Kolodner R D
Ludwig Institute for Cancer Research, University of California-San Diego School of Medicine, La Jolla 92093, USA.
Mol Cell. 1998 Jul;2(1):9-22. doi: 10.1016/s1097-2765(00)80109-4.
Three temperature-sensitive S. cerevisiae RFA1 alleles were found to cause elevated mutation rates. These mutator phenotypes resulted from the accumulation of base substitutions, frameshifts, gross deletions (8 bp-18 kb), and nonreciprocal translocations. A representative rfa1 mutation exhibited a growth defect in conjunction with rad51, rad52, or rad10 mutations, suggesting an accumulation of double-strand breaks. rad10 and rad52 mutations eliminated deletion and translocation formation, whereas a rad51 mutation increased the frequency of these events and revealed a new class of genetic rearrangements--loss of a portion of a chromosome arm combined with telomere addition. The breakpoints of the translocations and deletions were flanked by imperfect direct repeats of 2-20 bp, similar to the breakpoint structures observed at translocations and gross deletions, including LOH events, underlying human cancer and other hereditary diseases.
发现三个温度敏感型酿酒酵母RFA1等位基因会导致突变率升高。这些突变体表型是由碱基替换、移码、大片段缺失（8 bp - 18 kb）和非相互易位的积累引起的。一个代表性的rfa1突变与rad51、rad52或rad10突变一起表现出生长缺陷，表明双链断裂的积累。rad10和rad52突变消除了缺失和易位的形成，而rad51突变增加了这些事件的频率，并揭示了一类新的基因重排——染色体臂的一部分缺失并伴有端粒添加。易位和缺失的断点两侧是2 - 20 bp的不完全直接重复序列，类似于在包括人类癌症和其他遗传性疾病在内的易位和大片段缺失（包括杂合性丢失事件）中观察到的断点结构。
