Vallur Aarthy C, Maizels Nancy
Departments of Immunology and Biochemistry, University of Washington Medical School, Seattle, WA 98195-7650, USA.
Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16508-12. doi: 10.1073/pnas.0805327105. Epub 2008 Oct 21.
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.
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）基因类别转换重组和体细胞超突变中发挥作用。该酶在体外具有5'-3'外切核酸酶、瓣状内切核酸酶和较弱的核糖核酸酶H活性，但一直难以将这些活性与其多样的生物学功能相协调。我们报告了人外切核酸酶1对具有形成G环和G4 DNA潜力的转录富含G的DNA序列有强大的切割作用。预测的Ig类别转换重组中间体是外切核酸酶和5'瓣状内切核酸酶切割的底物。切除是切口依赖性和结构依赖性的。这些结果导致了一个外切核酸酶1在类别转换重组中功能的模型，其中在激活诱导脱氨酶（AID）引发的切口处的切割产生缺口，这些缺口成为AID进一步攻击和后续修复的底物。
