Chmielewski Jeffrey P, Henderson Laura, Smith Charlotte M, Christensen Tim W
Department of Biology, East Carolina University, Greenville, NC 27858, USA.
Chromosoma. 2012 Dec;121(6):585-96. doi: 10.1007/s00412-012-0383-8. Epub 2012 Sep 20.
The condensation state of chromosomes is a critical parameter in multiple processes within the cell. Failures in the maintenance of appropriate condensation states may lead to genomic instability, mis-expression of genes, and a number of disease states. During cell proliferation, replication of DNA represents an ongoing challenge for chromosome packaging as DNA must be unpackaged for replication and then faithfully repackaged. An integral member of the DNA replication machinery is the GINS complex which has been shown to stabilize the CMG complex which is required for processivity of the Mcm2-7 helicase complex during S phase. Through examination of the phenotypes associated with a null mutation in Psf2, a member of the evolutionarily conserved GINS complex, we find that Drosophila Psf2 likely has a role in establishing chromosome condensation and that the defects associated with this mis-condensation impact M phase progression, genomic stability, and transcriptional regulation.
染色体的凝聚状态是细胞内多个过程中的关键参数。维持适当凝聚状态失败可能导致基因组不稳定、基因错误表达以及多种疾病状态。在细胞增殖过程中,DNA复制对染色体包装来说是一项持续的挑战,因为DNA必须解包以进行复制,然后再忠实地重新包装。DNA复制机制的一个重要成员是GINS复合物,已证明它能稳定CMG复合物,而CMG复合物是S期Mcm2 - 7解旋酶复合物持续合成所必需的。通过研究与进化保守的GINS复合物成员Psf2基因敲除突变相关的表型,我们发现果蝇Psf2可能在建立染色体凝聚中起作用,并且与这种错误凝聚相关的缺陷会影响M期进程、基因组稳定性和转录调控。