Ben-Aroya Shay, Koren Amnon, Liefshitz Batia, Steinlauf Rivka, Kupiec Martin
Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel.
Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9906-11. doi: 10.1073/pnas.1633757100. Epub 2003 Aug 8.
Many overlapping surveillance and repair mechanisms operate in eukaryotic cells to ensure the stability of the genome. We have screened to isolate yeast mutants exhibiting increased levels of recombination between repeated sequences. Here we characterize one of these mutants, elg1. Strains lacking Elg1p exhibit elevated levels of recombination between homologous and nonhomologous chromosomes, as well as between sister chromatids and direct repeats. These strains also exhibit increased levels of chromosome loss. The Elg1 protein shares sequence homology with the large subunit of the clamp loader replication factor C (RFC) and with the product of two additional genes involved in checkpoint functions and genome maintenance: RAD24 and CTF18. Elg1p forms a complex with the Rfc2-5 subunits of RFC that is distinct from the previously described RFC-like complexes containing Rad24 and Ctf18. Genetic data indicate that the Elg1, Ctf18, and Rad24 RFC-like complexes work in three separate pathways important for maintaining the integrity of the genome and for coping with various genomic stresses.
真核细胞中存在许多重叠的监测和修复机制,以确保基因组的稳定性。我们进行了筛选,以分离出在重复序列之间重组水平增加的酵母突变体。在此,我们对其中一个突变体elg1进行了表征。缺乏Elg1p的菌株在同源和非同源染色体之间以及姐妹染色单体和直接重复序列之间表现出升高的重组水平。这些菌株还表现出增加的染色体丢失水平。Elg1蛋白与钳位装载器复制因子C(RFC)的大亚基以及另外两个参与检查点功能和基因组维持的基因产物具有序列同源性:RAD24和CTF18。Elg1p与RFC的Rfc2-5亚基形成复合物,该复合物不同于先前描述的含有Rad24和Ctf18的类RFC复合物。遗传数据表明,Elg1、Ctf18和Rad24类RFC复合物在维持基因组完整性和应对各种基因组应激的三个独立途径中发挥作用。