Darwiche N, Freeman L A, Strunnikov A
Unit of Chromosome Structure and Function, NIH, NICHD, Laboratory of Molecular Embryology, 18T Library Drive, room 106, Bethesda, MD 20892-5430, USA.
Gene. 1999 Jun 11;233(1-2):39-47. doi: 10.1016/s0378-1119(99)00160-2.
Establishing and maintaining proper sister chromatid cohesion throughout the cell cycle are essential for maintaining genome integrity. To understand how sister chromatid cohesion occurs in mammals, we have cloned and characterized mouse orthologs of proteins known to be involved in sister chromatid cohesion in other organisms. The cDNAs for the mouse orthologs of SMC1S.c. and SMC3S.c. , mSMCB and mSMCD respectively, were cloned, and the corresponding transcripts and proteins were characterized. mSMCB and mSMCD are transcribed at similar levels in adult mouse tissues except in testis, which has an excess of mSMCD transcripts. The mSMCB and mSMCD proteins, as well as the PW29 protein, a mouse homolog of Mcd1pS.c./Rad21S.p., form a complex similar to cohesin in X. laevis. mSMCB, mSMCD and PW29 protein levels show no significant cell-cycle dependence. The bulk of the mSMCB, mSMCD and PW29 proteins undergo redistribution from the chromosome vicinity to the cytoplasm during prometaphase and back to the chromatin in telophase. This pattern of intracellular localization suggests a complex role for this group of SMC proteins in chromosome dynamics. The PW29 protein and PCNA, which have both been implicated in sister chromatid cohesion, do not colocalize, indicating that these proteins may not function in the same cohesion pathway. Overexpression of a PW29-GFP fusion protein in mouse fibroblasts leads to inhibition of proliferation, implicating this protein and its complex with SMC proteins in the control of mitotic cycle progression.
在整个细胞周期中建立并维持适当的姐妹染色单体黏连对于维持基因组完整性至关重要。为了解哺乳动物中姐妹染色单体黏连是如何发生的，我们克隆并鉴定了已知在其他生物体中参与姐妹染色单体黏连的蛋白质的小鼠直系同源物。分别克隆了SMC1S.c.和SMC3S.c.的小鼠直系同源物mSMCB和mSMCD的cDNA，并对相应的转录本和蛋白质进行了鉴定。mSMCB和mSMCD在成年小鼠组织中的转录水平相似，但在睾丸中除外，睾丸中有过量的mSMCD转录本。mSMCB和mSMCD蛋白，以及Mcd1pS.c./Rad21S.p.的小鼠同源物PW29蛋白，形成了一个类似于非洲爪蟾中黏连蛋白的复合物。mSMCB、mSMCD和PW29蛋白水平没有明显的细胞周期依赖性。在有丝分裂前期，大部分mSMCB、mSMCD和PW29蛋白从染色体附近重新分布到细胞质中，并在末期回到染色质上。这种细胞内定位模式表明这组SMC蛋白在染色体动态变化中具有复杂的作用。PW29蛋白和PCNA都与姐妹染色单体黏连有关，但它们并不共定位，这表明这些蛋白可能不在同一条黏连途径中发挥作用。在小鼠成纤维细胞中过表达PW29-GFP融合蛋白会导致增殖受到抑制，这表明该蛋白及其与SMC蛋白的复合物参与了有丝分裂周期进程的调控。
