Although most cells maintain a constant size as they proliferate, it remains unclear how the cell cycle progression is coupled to increases in cell mass. We have previously identified a DNA-binding protein, Translin, whose native form consists of a ring-shaped structure with an assembly of eight 27-kD monomer subunits. This multimeric structure creates a DNA-binding domain for the sequences at breakpoint junctions in many chromosomal translocations. The region around the Translin gene on human chromosome 2q21 also harbors the ERCC3 gene, which is known to be involved in human disorders of DNA repair. Despite detailed studies on protein–DNA interactions, the functional significance of Translin remains unknown. In studies comparing basal expression levels of Translin across various tissues and cell lines, we have found a good correlation between Translin protein synthesis and cell proliferation. To analyze the effect of Translin on cell proliferation, we established a Translin expression system regulatable by doxycycline. We found that overexpression of Translin in HEK293 cells increased cell proliferation by two- to threefold. Flow-cytometric forward-scatter analysis revealed that the size of the cells was increased compared with the control cells that grew in the absence of doxycycline. These results indicate that Translin may be involved in cell cycle progression and that its overexpression accelerates cell division independent of increases in cell mass.