Rad27 和 Exo1 在酿酒酵母错配修复的不同切除途径中发挥作用。
Rad27 and Exo1 function in different excision pathways for mismatch repair in Saccharomyces cerevisiae.
机构信息
Ludwig Institute for Cancer Research, University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0660, USA.
Departments of Medicine, University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0660, USA.
出版信息
Nat Commun. 2021 Sep 22;12(1):5568. doi: 10.1038/s41467-021-25866-z.
Eukaryotic DNA Mismatch Repair (MMR) involves redundant exonuclease 1 (Exo1)-dependent and Exo1-independent pathways, of which the Exo1-independent pathway(s) is not well understood. The exo1Δ440-702 mutation, which deletes the MutS Homolog 2 (Msh2) and MutL Homolog 1 (Mlh1) interacting peptides (SHIP and MIP boxes, respectively), eliminates the Exo1 MMR functions but is not lethal in combination with rad27Δ mutations. Analyzing the effect of different combinations of the exo1Δ440-702 mutation, a rad27Δ mutation and the pms1-A99V mutation, which inactivates an Exo1-independent MMR pathway, demonstrated that each of these mutations inactivates a different MMR pathway. Furthermore, it was possible to reconstitute a Rad27- and Msh2-Msh6-dependent MMR reaction in vitro using a mispaired DNA substrate and other MMR proteins. Our results demonstrate Rad27 defines an Exo1-independent eukaryotic MMR pathway that is redundant with at least two other MMR pathways.
真核生物 DNA 错配修复（MMR）涉及冗余的核酸外切酶 1（Exo1）依赖性和 Exo1 非依赖性途径，其中 Exo1 非依赖性途径（s）尚未得到很好的理解。exo1Δ440-702 突变，缺失 MutS Homolog 2（Msh2）和 MutL Homolog 1（Mlh1）相互作用肽（SHIP 和 MIP 盒，分别），消除了 Exo1 MMR 功能，但与 rad27Δ 突变结合并不致命。分析不同组合的 exo1Δ440-702 突变、rad27Δ 突变和 pms1-A99V 突变（失活 Exo1 非依赖性 MMR 途径）的效果，表明这些突变中的每一种都失活了不同的 MMR 途径。此外，使用错配 DNA 底物和其他 MMR 蛋白，有可能在体外重建 Rad27 和 Msh2-Msh6 依赖性 MMR 反应。我们的结果表明 Rad27 定义了一种 Exo1 非依赖性真核 MMR 途径，该途径与至少两种其他 MMR 途径冗余。
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