Department of Biology, East Carolina University East Carolina University, Greenville, NC 27858, USA.
Biochem Biophys Res Commun. 2010 Sep 10;400(1):145-50. doi: 10.1016/j.bbrc.2010.08.033. Epub 2010 Aug 13.
Essential for the normal functioning of a cell is the maintenance of genomic integrity. Failure in this process is often catastrophic for the organism, leading to cell death or mis-proliferation. Central to genomic integrity is the faithful replication of DNA during S phase. The GINS complex has recently come to light as a critical player in DNA replication through stabilization of MCM2-7 and Cdc45 as a member of the CMG complex which is likely responsible for the processivity of helicase activity during S phase. The GINS complex is made up of 4 members in a 1:1:1:1 ratio: Psf1, Psf2, Psf3, And Sld5. Here we present the first analysis of the function of the Sld5 subunit in a multicellular organism. We show that Drosophila Sld5 interacts with Psf1, Psf2, and Mcm10 and that mutations in Sld5 lead to M and S phase delays with chromosomes exhibiting hallmarks of genomic instability.
维持基因组完整性对于细胞的正常功能至关重要。如果这个过程失败,通常对生物体是灾难性的,会导致细胞死亡或异常增殖。基因组完整性的核心是在 S 期忠实复制 DNA。GINS 复合物最近被发现是 DNA 复制的关键参与者,通过稳定 MCM2-7 和 Cdc45 作为 CMG 复合物的成员,CMG 复合物可能负责 S 期解旋酶活性的连续性。GINS 复合物由 4 个成员以 1:1:1:1 的比例组成:Psf1、Psf2、Psf3 和 Sld5。在这里,我们首次分析了 Sld5 亚基在多细胞生物中的功能。我们表明,果蝇 Sld5 与 Psf1、Psf2 和 Mcm10 相互作用,并且 Sld5 的突变导致 M 和 S 期延迟,染色体表现出基因组不稳定性的特征。