Chromosomal rearrangements occur in S-cerevisiae rfa1 mutator mutants due to mutagenic lesions processed by double-strand-break repair
Chromosomal rearrangements occur in S-cerevisiae rfa1 mutator mutants due to mutagenic lesions processed by double-strand-break repair
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DOI：
10.1016/s1097-2765(00)80109-4
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发表时间：
1998-07-01
期刊：
影响因子：
16
通讯作者：
Kolodner, RD
中科院分区：
文献类型：
--
作者：
Chen, C;Umezu, K;Kolodner, RD
三个温敏S.发现酿酒酵母RFA 1等位基因导致突变率升高。这些增变基因表型是由碱基替换、移码、总缺失（8 bp-18 kb）和非相互易位的积累引起的。代表性的rfa 1突变与rad 51、rad 52或rad 10突变一起表现出生长缺陷，表明双链断裂的积累。RAD 10和RAD 52突变消除了缺失和易位形成，而RAD 51突变增加了这些事件的频率，并揭示了一类新的遗传重排-染色体臂的一部分丢失与端粒增加相结合。易位和缺失的断裂点两侧是2-20 bp的不完全同向重复序列，类似于在易位和总缺失处观察到的断裂点结构，包括洛事件，潜在的人类癌症和其他遗传性疾病。
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.