酿酒酵母中主要人类AP核酸内切酶HAP1的同源物APN2的鉴定及其在无碱基位点修复中的作用。
Identification of APN2, the Saccharomyces cerevisiae homolog of the major human AP endonuclease HAP1, and its role in the repair of abasic sites.
作者信息
Johnson R E, Torres-Ramos C A, Izumi T, Mitra S, Prakash S, Prakash L
机构信息
Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555-1061, USA.
出版信息
Genes Dev. 1998 Oct 1;12(19):3137-43. doi: 10.1101/gad.12.19.3137.
Abstract
Abasic (AP) sites arise in DNA through spontaneous base loss and enzymatic removal of damaged bases. APN1 encodes the major AP-endonuclease of Saccharomyces cerevisiae. Human HAP1 (REF1) encodes the major AP endonuclease which, in addition to its role in DNA repair, functions as a redox regulatory protein. We identify APN2, the yeast homolog of HAP1 and provide evidence that Apn1 and Apn2 represent alternate pathways for repairing AP sites. The apn1Delta apn2Delta strain displays a highly elevated level of MMS-induced mutagenesis, which is dependent on the REV3, REV7, and REV1 genes. Our findings indicate that AP sites are highly cytotoxic and mutagenic in eukaryotes, and that the REV3, REV7-encoded DNA polymerase zeta mediates the mutagenic bypass of AP sites.
摘要
脱碱基（AP）位点通过自发碱基丢失和酶促去除受损碱基而在DNA中产生。APN1编码酿酒酵母的主要AP内切核酸酶。人类HAP1（REF1）编码主要的AP内切核酸酶，它除了在DNA修复中发挥作用外，还作为一种氧化还原调节蛋白发挥功能。我们鉴定出了HAP1的酵母同源物APN2，并提供证据表明Apn1和Apn2代表修复AP位点的替代途径。apn1Delta apn2Delta菌株显示出MMS诱导的诱变水平高度升高，这依赖于REV3、REV7和REV1基因。我们的研究结果表明，AP位点在真核生物中具有高度细胞毒性和诱变性，并且REV3、REV7编码的DNA聚合酶ζ介导了AP位点的诱变旁路。
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