by Pur-alpha's ability to bind nucleic acids coupled to its ability to interact with regulatory and transport proteins. Relevance in human diseases Genetic perturbation in leukemia and anti-proliferative effect PURA, located at chromosome 5 band q31, is frequently deleted in myelodysplastic syndrome (MDS), a disorder of white blood cells, that may progress to acute myelogenous leukemia (AML). Loss of one copy of chromosome 7 is also frequent in MDS. PURB, the gene encoding Pur-beta, is located at 7p13. A visual fluorescence analysis of chromosomes from MDS patients shows that deletions of PURA at 5q31 are more strongly linked to progression of MDS to AML when combined with deletions of the PURB gene, including complete loss of chromosome 7. All of the PURA deletions noted, involve only one of the two paired, parentally-derived chromosomes. The implication is that Pur-alpha and -beta are each codominantly expressed, and that haploid levels are insufficient for a protective effect against cancer. All known PURA deletions in people occur in only one of the two copies of chromosome 5. Inducing increased levels of Pur-alpha in several different cultured cancer cell lines blocks cell proliferation. It also blocks anchorage-independent colony formation, a hallmark of cancer. This is true whether Pur-alpha is microinjected or expressed after introducing a cloned PURA cDNA into cells. The Pur-alpha inhibition of cancer cell proliferation occurs at specific points in the cell division cycle, primarily at checkpoints for transition to DNA replication or mitosis. These cell cycle effects are consistent with an interaction between Pur-alpha and CDK, cell cycle-dependent protein kinases. They are also consistent with documented interaction between Pur-alpha and the tumor suppressor protein, Rb. Role in mammalian brain development and neurological diseases Studies of genetic inactivation of PURA in the mouse provided evidence leading to that for PURA gene disorders in brain disease. Homozygous PURA knockouts die shortly after birth with severe defects in brain layer development, tissue wasting and movement disorders. Defects in blood cell development are also prominent, and it is not known how these may affect the brain. Heterozygous knockouts do not die early but exhibit seizure-like disorders. In rat hippocampal neurons, Pur-alpha is found in the cytoplasm together with mRNA transcripts, in a complex including non-coding RNAs, Pur-beta, fragile X mental retardation proteins and microtubule-associated proteins. This complex is transported by a kinesin motor to sites of translation at junctions of nerve cell dendrites. Recently PURA mutations