Schmiesing J A, Ball A R, Gregson H C, Alderton J M, Zhou S, Yokomori K
Department of Biological Chemistry, College of Medicine, 240 D Medical Sciences I, University of California, Irvine, CA 92697-1700, USA.
Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):12906-11. doi: 10.1073/pnas.95.22.12906.
The structural maintenance of chromosomes (SMC) family member proteins previously were shown to play a critical role in mitotic chromosome condensation and segregation in yeast and Xenopus. Other family members were demonstrated to be required for DNA repair in yeast and mammals. Although several different SMC proteins were identified in different organisms, little is known about the SMC proteins in humans. Here, we report the identification of four human SMC proteins that form two distinct heterodimeric complexes in the cell, the human chromosome-associated protein (hCAP)-C and hCAP-E protein complex (hCAP-C/hCAP-E), and the human SMC1 (hSMC1) and hSMC3 protein complex (hSMC1/hSMC3). The hCAP-C/hCAP-E complex is the human ortholog of the Xenopus chromosome-associated protein (XCAP)-C/XCAP-E complex required for mitotic chromosome condensation. We found that a second complex, hSMC1/hSMC3, is required for metaphase progression in mitotic cells. Punctate vs. diffuse distribution patterns of the hCAP-C/hCAP-E and hSMC1/hSMC3 complexes in the interphase nucleus indicate independent behaviors of the two complexes during the cell cycle. These results suggest that two distinct classes of SMC protein complexes are involved in different aspects of mitotic chromosome organization in human cells.
染色体结构维持（SMC）家族成员蛋白先前已被证明在酵母和非洲爪蟾的有丝分裂染色体凝聚和分离过程中发挥关键作用。其他家族成员被证明是酵母和哺乳动物DNA修复所必需的。尽管在不同生物体中鉴定出了几种不同的SMC蛋白，但对人类中的SMC蛋白却知之甚少。在此，我们报告鉴定出四种人类SMC蛋白，它们在细胞中形成两种不同的异二聚体复合物，即人类染色体相关蛋白（hCAP）-C和hCAP-E蛋白复合物（hCAP-C/hCAP-E），以及人类SMC1（hSMC1）和hSMC3蛋白复合物（hSMC1/hSMC3）。hCAP-C/hCAP-E复合物是有丝分裂染色体凝聚所需的非洲爪蟾染色体相关蛋白（XCAP）-C/XCAP-E复合物的人类同源物。我们发现，第二种复合物hSMC1/hSMC3是有丝分裂细胞中期进程所必需的。hCAP-C/hCAP-E和hSMC1/hSMC3复合物在间期细胞核中的点状与弥散分布模式表明这两种复合物在细胞周期中具有独立行为。这些结果表明，两类不同的SMC蛋白复合物参与了人类细胞有丝分裂染色体组织的不同方面。
