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RNA-templated DNA repair

机译：RNA模板DNA修复

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摘要

RNA can act as a template for DNA synthesis in the reverse transcription of retroviruses and retrotransposons1 and in the elongation of telomeres2. Despite its abundance in the nucleus, there has been no evidence for a direct role of RNA as a template in the repair of any chromosomal DNA lesions, including DNA double-strand breaks (DSBs), which are repaired in most organisms by homologous recombination or by non-homologous end joining. An indirect role for RNA in DNA repair, following reverse transcription and formation of a complementary DNA, has been observed in the non-homologous joining of DSB ends. In the yeast Saccharomyces cerevisiae, in which homologous recombination is efficient, RNA was shown to mediate recombination, but only indirectly through a cDNA intermediate generated by the reverse transcriptase function of Ty retrotransposons in Ty particles in the cytoplasm. Although pairing between duplex DNA and single-strand (ss)RNA can occur in vitro and in vivo, direct homologous exchange of genetic information between RNA and DNA molecules has not been observed. We show here that RNA can serve as a template for DNA synthesis during repair of a chromosomal DSB in yeast. The repair was accomplished with RNA oligonucleotides complementary to the broken ends. This and the observation that even yeast replicative DNA polymerases such as a and 5 can copy short RNA template tracts in vitro demonstrate that RNA can transfer genetic information in vivo through direct homologous interaction with chromosomal DNA.
机译：RNA可以在逆转录病毒和逆转座子1的逆转录以及端粒2的延伸中充当DNA合成的模板。尽管其在细胞核中丰富，但尚无证据表明RNA作为模板可直接修复任何染色体DNA损伤，包括DNA双链断裂（DSB），而DNA在大多数生物体中均通过同源重组或通过非同源末端连接。在DSB末端的非同源连接中，逆转录和形成互补DNA后，RNA在DNA修复中具有间接作用。在酵母酿酒酵母中，同源重组是有效的，显示RNA介导重组，但仅间接通过由胞质中Ty颗粒中Ty逆转录转座子的逆转录酶功能产生的cDNA中间产物间接介导。尽管双链DNA和单链（ss）RNA之间的配对可以在体外和体内进行，但尚未观察到RNA和DNA分子之间遗传信息的直接同源交换。我们在这里表明，RNA可以作为酵母中染色体DSB修复过程中DNA合成的模板。用与断裂末端互补的RNA寡核苷酸完成修复。这以及观察到即使酵母复制性DNA聚合酶（如a和5）也可以在体外复制短RNA模板片段，这表明RNA可以通过与染色体DNA的直接同源相互作用在体内转移遗传信息。

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