Human Mus81-associated endonuclease cleaves holliday junctions in vitro
Human Mus81-associated endonuclease cleaves holliday junctions in vitro
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DOI：
10.1016/s1097-2765(01)00375-6
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发表时间：
2001-11-01
期刊：
影响因子：
16
通讯作者：
McGowan, CH
中科院分区：
文献类型：
--
作者：
Chen, XB;Melchionna, R;McGowan, CH
Mus 81是一种与ERCC 1-XPF核酸内切酶的XPF亚基具有同源性的蛋白质，对于芽殖酵母和裂殖酵母的复制应激耐受性都是重要的。人Mus 8l具有针对结构特异性寡核苷酸底物的相关核酸内切酶活性，包括合成的霍利迪连接。Mus 81相关的核酸内切酶通过仅在相同极性的链上切割交叉点，将霍利迪连接点分解为线性双链体。此外，在暴露于阻断DNA复制的试剂后，细胞中的Mus 8l蛋白丰度增加。总之，这些发现表明Mus 8l在解决当DNA复制被损伤或核苷酸耗尽阻断时出现的霍利迪连接中的作用。Mus 8l与先前表征的霍利迪连接解析酶的序列无关，并且它具有不同的酶性质，这表明它使用新的酶策略来切割霍利迪连接。
Mus81, a protein with homology to the XPF subunit of the ERCC1-XPF endonuclease, is important for replicational stress tolerance in both budding and fission yeast. Human Mus8l has associated endonuclease activity against structure-specific oligonucleotide substrates, including synthetic Holliday junctions. Mus81-associated endonuclease resolves Holliday junctions into linear duplexes by cutting across the junction exclusively on strands of like polarity. In addition, Mus8l protein abundance increases in cells following exposure to agents that block DNA replication. Taken together, these findings suggest a role for Mus8l in resolving Holliday junctions that arise when DNA replication is blocked by damage or by nucleotide depletion. Mus8l is not related by sequence to previously characterized Holliday junction resolving enzymes, and it has distinct enzymatic properties that suggest it uses a novel enzymatic strategy to cleave Holliday junctions.