Characterization of a novel human SMC heterodimer homologous to the Schizosaccharomyces pombe Rad18/Apr18 complex

The structural maintenance of chromosomes (SMC) protein encoded by the fiss ion yeast rad18 gene is involved in several DNA repair processes and has an essential function in DNA replication and mitotic control. It has a hetero dimeric partner SMC protein, Spr18, with which it forms the core of a multi protein complex. We have now isolated the human orthologues of rad18 and sp r18 and designated them hSMC6 and hSMC5. Both proteins are about 1100 amino acids in length and are 27-28% identical to their fission yeast orthologue s, with much greater identity within their Nand C-terminal globular domains . The hSMC6 and hSMC5 proteins interact to form a tight complex analogous t o the yeast Rad18/Spr18 heterodimer. In proliferating human cells the prote ins are bound to both chromatin and the nucleoskeleton. In addition, we hav e 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.