title: Nuclear proteins binding to the recombination hotspot region of the retinoic acid receptor alpha gene.
abstract: Acute promyelocytic leukemia (APL) has been characterized by 15;17 chromosomal translocation, which involves the retinoic acid receptor alpha (RARA) gene on chromosome 17 and the PML gene on chromosome 15. An extremely restricted region (ERR) of 50 bps within the second intron of the RARA gene was identified as the cluster region of breakpoints by sequencing analyses. ERR was tested by in vitro transfection-recombination assay, and was shown to be the recombination hot spot. In this study, presence of DNA binding proteins to the 148 bps DNA fragment which contains ERR was confirmed by gel-mobility shift analysis in the nuclear extract of NIH3T3 cells and human leukemia cell lines. Furthermore, in vitro study with the mouse sarcoma cell lines using the recombination reporter plasmid containing ERR showed that ERR might be involved in the homologous recombination in addition to the illegitimate recombination. The DNA binding proteins specific to ERR might play an important role in chromosome translocation.
authors.affiliation: Department of Molecular Biology, School of Medicine, Hiroshima University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tashiro
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: N
authors.initials: N
authors.lastname: Kotomura
authors.forename: O
authors.initials: O
authors.lastname: Niwa
authors.forename: K
authors.initials: K
authors.lastname: Ueda
authors.forename: N
authors.initials: N
authors.lastname: Kamada
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D051379:Mice; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000235:genetics*; D011995:Recombination, Genetic; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D014178:Translocation, Genetic; D025521:Tumor Suppressor Proteins
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; C000607071:RARA protein, human; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human