Nucleolin is a major nucleolar phosphoprotein which is associated with preribosomal RNA and is implicated in the early stage of preribosomal RNP assembly and processing. This 100 kDa protein can be subdivided into three major domain: The N-terminal domain comprises long acidic stretches interspersed with basic repeats, similar to the structure of a high mobility group-type protein. This domain is responsible for the ability of nucleolin to modulate chromatin condensation. In contrast, the central domain contains four RNA binding elements. Finally, the C-terminal domain, approximately 85 amino acids long, is strikingly rich in glycine, arginine, and phenylalanine residues. Nucleolin fluctuates in parallel to DNA synthesis. The intact 100 kDa nucleolin molecule is the major species in actively dividing cells, whereas the degraded forms are relatively abundant in nondividing cells. Stability of nucleolin molecule is cell proliferation-dependent. Nucleolin is found to be identical to the human DNA helicase IV. Nucleolin/DNA helicase IV can unwind RNA-RNA duplexes, as well as DNA-DNA and DNA-RNA duplexes. Furthermore, nucleolin directly interacts with DNA topoisomerase I.