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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Activities Of Human Exonuclease 1 That Promote Cleavage Of Transcribed Immunoglobulin Switch Regions
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Activities Of Human Exonuclease 1 That Promote Cleavage Of Transcribed Immunoglobulin Switch Regions

机译：促进转录的免疫球蛋白开关区切割的人类核酸外切酶1的活动。

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摘要

Eukaryotic exonuclease 1 functions in replication, recombination, mismatch repair, telomere maintenance, immunoglobulin (Ig) gene class switch recombination, and somatic hypermutation. The enzyme has 5'-3' exonuclease, flap endonuclease, and weak RNaseH activity in vitro, but it has been difficult to reconcile these activities with its diverse biological functions. We report robust cleavage by human exonuclease 1 of transcribed G-rich DNA sequences with potential to form G loops and G4 DNA. Predicted Ig switch recombination intermediates are substrates for both exonucleolytic and 5' flap endonucleolytic cleavage. Excision is nick-dependent and structure-dependent. These results lead to a model for exonuclease 1 function in class switch recombination in which cleavage at activation-induced deaminase (AID)-initiated nicks produces gaps that become substrates for further attack by AID and subsequent repair.
机译：真核外切核酸酶1在复制，重组，错配修复，端粒维持，免疫球蛋白（Ig）基因类别开关重组和体细胞超突变中起作用。该酶在体外具有5'-3'核酸外切酶，皮瓣内切核酸酶和弱的RNaseH活性，但是很难用多种生物学功能调节这些活性。我们报告了人类外切核酸酶1转录的富含G的DNA序列的强大切割，可能形成G环和G4 DNA。预测的Ig开关重组中间体是核酸外切和5'瓣内切核酸裂解的底物。切除依赖切口和结构。这些结果导致了核酸外切酶1在类别开关重组中起作用的模型，其中在激活诱导的脱氨酶（AID）引发的切口处产生的切割产生缺口，这些缺口成为AID进一步攻击和后续修复的底物。

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