The human F-Box DNA helicase FBH1 faces Saccharomyces cerevisiae Srs2 and postreplication repair pathway roles
The human F-Box DNA helicase FBH1 faces Saccharomyces cerevisiae Srs2 and postreplication repair pathway roles
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DOI：
10.1128/mcb.00963-07
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发表时间：
2007-11-01
影响因子：
5.3
通讯作者：
Liberi, Giordano
中科院分区：
文献类型：
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作者：
Chiolo, Irene;Saponaro, Marco;Liberi, Giordano
酿酒酵母Srs2 UvrD DNA解旋酶通过防止计划外重组事件控制基因组完整性。虽然Srs2的同源基因已经在原核生物和低等真核生物中被发现，但到目前为止，人类Srs2的同源基因还没有被描述。我们发现人类F-box DNA解旋酶hFBH1抑制了葡萄球菌srs2突变体的特异性重组缺陷，这与hFBH1解旋酶结构域与srs2高度保守的发现一致。令人惊讶的是，在SRS2缺失的情况下，hFBH1也会抑制由复制后修复依赖功能失活导致的DNA损伤敏感性，从而导致PCNA泛素化。hFBH1的F-box结构域不存在于Srs2中，对于hFBH1替代Srs2和复制后修复因子的功能至关重要。此外，我们的研究结果表明，完整的F-box结构域作为SCF泛素连接酶，是DNA损伤诱导的hFBH1自身降解所必需的。总之，我们的研究结果表明hFBH1解旋酶是出芽酵母Srs2的功能性人类同源物，也具有执行其重组功能所必需的自我调节特性。
The Saccharomyces cerevisiae Srs2 UvrD DNA helicase controls genome integrity by preventing unscheduled recombination events. While Srs2 orthologues have been identified in prokaryotic, and lower eukaryotic organisms, human orthologues of Srs2 have not been described so far. We found that the human F-box DNA helicase hFBH1 suppresses specific recombination defects of S. cerevisiae srs2 mutants, consistent with the finding that the helicase domain of hFBH1 is highly conserved with that of Srs2. Surprisingly, hFBH1 in the absence of SRS2 also suppresses the DNA damage sensitivity caused by inactivation of postreplication repairdependent functions leading to PCNA ubiquitylation. The F-box domain of hFBH1, which is not present in Srs2, is crucial for hFBH1 functions in substituting for Srs2 and postreplication repair factors. Furthermore, our findings indicate that an intact F-box domain, acting as an SCF ubiquitin ligase, is required for the DNA damage-induced degradation of hFBH1 itself. Overall, our findings suggest that the hFBH1 helicase is a functional human orthologue of budding yeast Srs2 that also possesses self-regulation properties necessary to execute its recombination functions.