NUCLEAR PROTEINS BINDING TO THE RECOMBINATION HOT-SPOT REGION OF THE RETINOIC ACID RECEPTOR-ALPHA GENE

Acute promyelocytic leukemia (APL) has been characterized by 15; 17 ch romosomal translocation, which involves the retinoic acid receptor alp ha (RARA) gene on chromosome 17 and the PML gene on chromosome 15. An extremely restricted region (ERR) of 50 bps within the second intron o f the RARA gene was identified as the cluster region of breakpoints by sequencing analyses. ERR was tested by in vitro transfection-recombin ation assay, and was shown to be the recombination hot spot. In this s tudy, presence of DNA binding proteins to the 148 bps DNA fragment whi ch contains ERR was confirmed by gel-mobility shift analysis in the nu clear extract of NIH3T3 cells and human leukemia cell lines. Furthermo re, in vitro study with the mouse sarcoma cell lines using the recombi nation reporter plasmid containing ERR showed that ERR might be involv ed in the homologous recombination in addition to the illegitimate rec ombination. The DNA binding proteins specific to ERR might play an imp ortant role in chromosome translocation.