SMC1 - AN ESSENTIAL YEAST GENE ENCODING A PUTATIVE HEAD-ROD-TAIL PROTEIN IS REQUIRED FOR NUCLEAR DIVISION AND DEFINES A NEW UBIQUITOUS PROTEIN FAMILY

The smc1-1 mutant was identified initially as a mutant of Saccharomyce s cerevisiae that had an elevated rate of minichromosome nondisjunctio n. We have cloned the wild-type SMC1 gene. The sequence of the SMC1 ge ne predicts that its product (Smc1p) is a 141-kD protein, and antibodi es against Smc1 protein detect a protein with mobility of 165 kD. Anal ysis of the primary and putative secondary structure of Smc1p suggests that it contains two central coiled-coil regions flanked by an amino- terminal nucleoside triphosphate (NTP)-binding head and a conserved ca rboxy-terminal tail. These analyses also indicate that Smc1p is an evo lutionary conserved protein and is a member of a new family of protein s ubiquitous among prokaryotes and eukaryotes. The SMC1 gene is essent ial for viability. Several phenotypic characteristics of the mutant al leles of smc1 gene indicate that its product is involved in some aspec ts of nuclear metabolism, most likely in chromosome segregation. The s mc1-1 and smc1-2 mutants have a dramatic increase in mitotic loss of a chromosome fragment and chromosome III, respectively, but have no inc rease in mitotic recombination. Depletion of SMC1 function in the ts m utant, smc1-2, causes a dramatic mitosis-related lethality. Smc1p-depl eted cells have a defect in nuclear division as evidenced by the absen ce of anaphase cells. This phenotype of the smc1-2 mutant is not RAD9 dependent. Based upon the facts that Smc1p is a member of a ubiquitous family, and it is essential for yeast nuclear division, we propose th at Smc1p and Smc1p-like proteins function in a fundamental aspect of p rokaryotic and eukaryotic cell division.