Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
Cell Cycle. 2013 Aug 15;12(16):2570-9. doi: 10.4161/cc.25626. Epub 2013 Jul 10.
Maintaining genome stability is crucial for all cells. The budding yeast Elg1 protein, the major subunit of a replication factor C-like complex, is important for genome stability, since cells lacking Elg1 exhibit increased recombination and chromosomal rearrangements. This genome maintenance function of Elg1 seems to be conserved in higher eukaryotes, since removal of the human Elg1 homolog, encoded by the ATAD5 gene, also causes genome instability leading to tumorigenesis. The fundamental molecular function of the Elg1/ATAD5-replication factor C-like complex (RLC) was, until recently, elusive, although Elg1/ATAD5-RLC was known to interact with the replication sliding clamp PCNA. Two papers have now reported that following DNA replication, the Elg1/ATAD5-RLC is required to remove PCNA from chromatin in yeast and human cells. In this Review, we summarize the evidence that Elg1/ATAD5-RLC acts as a PCNA unloader and discuss the still enigmatic relationship between the function of Elg1/ATAD5-RLC in PCNA unloading and the role of Elg1/ATAD5 in maintaining genomic stability.
维持基因组稳定性对所有细胞都至关重要。芽殖酵母的 Elg1 蛋白是复制因子 C 样复合物的主要亚基，对基因组稳定性很重要，因为缺乏 Elg1 的细胞表现出增加的重组和染色体重排。Elg1 的这种基因组维持功能似乎在高等真核生物中保守，因为去除人 Elg1 的同源物（由 ATAD5 基因编码）也会导致基因组不稳定从而引发肿瘤形成。直到最近，Elg1/ATAD5-复制因子 C 样复合物（RLC）的基本分子功能仍然难以捉摸，尽管已知 Elg1/ATAD5-RLC 与复制滑动夹 PCNA 相互作用。现在有两篇论文报道，在 DNA 复制后，Elg1/ATAD5-RLC 被需要从酵母和人类细胞的染色质中去除 PCNA。在这篇综述中，我们总结了 Elg1/ATAD5-RLC 作为 PCNA 卸载器的证据，并讨论了 Elg1/ATAD5-RLC 在 PCNA 卸载中的功能与 Elg1/ATAD5 在维持基因组稳定性中的作用之间仍然神秘的关系。
