Mismatch repair (MMR) systems play important roles in maintaining the high fidelity of genomic DNA. It is well documented that a lack of MMR increases the mutation rate, including base exchanges and small insertion/deletion loops; however, it is unknown whether MMR deficiency affects the frequency of chromosomal recombination in somatic cells. To investigate the effects of MMR on chromosomal recombination, we used the Drosophila wing-spot test, which efficiently detects chromosomal recombination. We prepared MMR (MutS)-deficient flies (spel1(-/-)) using a fly line generated in this study. The spontaneous mutation rate as measured by the wing-spot test was slightly higher in MutS-deficient flies than in wild-type (spel1(+/-)) flies. Previously, we showed that N-nitrosodimethylamine (NDMA)-induced chromosomal recombination more frequently than N-nitrosodiethylamine (NDEA) in Drosophila. When the wing-spot test was performed using MMR-deficient flies, unexpectedly, the rate of NDMA-induced mutation was significantly lower in spel1(-/-) flies than in spel1(+/-) flies. In contrast, the rate of mutation induced by NDEA was higher in spel1(-/-) flies than in spel1(+/-) flies. These results suggest that in Drosophila, the MutS homologue protein recognises methylated DNA lesions more efficiently than ethylated ones, and that MMR might facilitate mutational chromosomal recombination due to DNA double-strand breaks via the futile cycle induced by MutS recognition of methylated lesions.

中文翻译：

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错配修复系统可能会促进果蝇中由N-亚硝基二甲胺（而不是N-亚硝基二乙胺）诱导的染色体重组。

错配修复（MMR）系统在维持基因组DNA的高保真度中起重要作用。有充分的证据表明，缺乏MMR会增加突变率，包括碱基交换和小的插入/缺失环。但是，MMR缺乏是否会影响体细胞中染色体重组的频率尚不清楚。为了研究MMR对染色体重组的影响，我们使用了果蝇翼点试验，该试验可有效检测染色体重组。我们使用这项研究中产生的飞行路线准备了MMR（MutS）缺陷果蝇（spel1（-/-））。通过机翼斑点测试测得的自发突变率在MutS缺陷型果蝇中略高于野生型（spel1（+/-））果蝇。先前，我们发现在果蝇中，N-亚硝基二甲胺（NDMA）诱导的染色体重组比N-亚硝基二乙胺（NDEA）更为频繁。当使用MMR缺陷果蝇进行翼点试验时，出乎意料的是，spel1（-/-）果蝇中NDMA诱导的突变率显着低于spel1（+/-）果蝇。相反，NDEA诱导的突变率在spel1（-/-）蝇中高于在spel1（+/-）蝇中。这些结果表明，在果蝇中，MutS同源蛋白比乙基化的更有效地识别甲基化的DNA损伤，并且MMR可能由于Muts识别甲基化的损伤而导致的DNA的双链断裂，导致DNA的双链断裂而促进了突变的染色体重组。出乎意料的是，spel1（-/-）果蝇中NDMA诱导的突变率显着低于spel1（+/-）果蝇中。相反，NDEA诱导的突变率在spel1（-/-）蝇中高于在spel1（+/-）蝇中。这些结果表明，在果蝇中，MutS同源蛋白比乙基化的更有效地识别甲基化的DNA损伤，并且MMR可能由于Muts识别甲基化的损伤而导致的DNA的双链断裂，导致DNA的双链断裂而促进了突变的染色体重组。出乎意料的是，spel1（-/-）果蝇中NDMA诱导的突变率显着低于spel1（+/-）果蝇中。相反，NDEA诱导的突变率在spel1（-/-）蝇中高于在spel1（+/-）蝇中。这些结果表明，在果蝇中，MutS同源蛋白比乙基化的更有效地识别甲基化的DNA损伤，并且MMR可能由于Muts识别甲基化的损伤而导致的DNA的双链断裂，导致DNA的双链断裂而促进了突变的染色体重组。