Taylor E M, Moghraby J S, Lees J H, Smit B, Moens P B, Lehmann A R
MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton BN1 9RR, United Kingdom.
Mol Biol Cell. 2001 Jun;12(6):1583-94. doi: 10.1091/mbc.12.6.1583.
The structural maintenance of chromosomes (SMC) protein encoded by the fission yeast rad18 gene is involved in several DNA repair processes and has an essential function in DNA replication and mitotic control. It has a heterodimeric partner SMC protein, Spr18, with which it forms the core of a multiprotein complex. We have now isolated the human orthologues of rad18 and spr18 and designated them hSMC6 and hSMC5. Both proteins are about 1100 amino acids in length and are 27-28% identical to their fission yeast orthologues, with much greater identity within their N- and C-terminal globular domains. The hSMC6 and hSMC5 proteins interact to form a tight complex analogous to the yeast Rad18/Spr18 heterodimer. In proliferating human cells the proteins are bound to both chromatin and the nucleoskeleton. In addition, we have detected a phosphorylated form of hSMC6 that localizes to interchromatin granule clusters. Both the total level of hSMC6 and its phosphorylated form remain constant through the cell cycle. Both hSMC5 and hSMC6 proteins are expressed at extremely high levels in the testis and associate with the sex chromosomes in the late stages of meiotic prophase, suggesting a possible role for these proteins in meiosis.
裂殖酵母rad18基因编码的染色体结构维持（SMC）蛋白参与多种DNA修复过程，在DNA复制和有丝分裂控制中具有重要功能。它有一个异源二聚体伙伴SMC蛋白Spr18，二者共同构成一个多蛋白复合体的核心。我们现已分离出rad18和spr18的人类同源物，并将它们命名为hSMC6和hSMC5。这两种蛋白长度均约为1100个氨基酸，与它们的裂殖酵母同源物有27% - 28%的同一性，在其N端和C端球状结构域内的同一性更高。hSMC6和hSMC5蛋白相互作用形成一个紧密复合体，类似于酵母Rad18/Spr18异源二聚体。在增殖的人类细胞中，这些蛋白与染色质和核骨架均有结合。此外，我们检测到一种定位于染色质间颗粒簇的磷酸化形式的hSMC6。hSMC6的总水平及其磷酸化形式在整个细胞周期中均保持恒定。hSMC5和hSMC6蛋白在睾丸中均有极高水平的表达，并在减数分裂前期后期与性染色体相关联，表明这些蛋白在减数分裂中可能发挥作用。
