Guanine-rich (GGNNGG) elements at chromosomal breakpoints interact with a loop-forming, single-stranded DNA-binding protein.
Proto-oncogene-activation is frequently preceded by chromosomal translocations. Several models suggest that DNA single-strands and loops may serve as intermediates in the process of illegitimate recombination. Guanine-rich, repetitive elements are preferred sites of chromosomal exchange and can undergo conformational changes which result in the generation of single-stranded DNA. Here we describe a single-stranded DNA-binding protein which binds specifically to guanine-rich elements at the breakpoints of human reciprocal translocations, including the t(14;18), t(2;8), t(9;22), t(15;17) and t(4;11) in leukemia and lymphoma. The primitive binding consensus consists of two guanine-residues on either side separated by a spacer of at least two nucleotides (GGN-NGG). Binding activity is unaltered by a spacer length of up to 46 nucleotides. These data suggest that the protein has the unique ability to form or stabilize DNA-loops and may thus play a general role in recombination.
Knapp
S
S
Department of Medicine I, University of Vienna, Austria.
Delle Karth
G
G
Friedl
J
J
Purtscher
B
B
Mitterbauer
G
G
Domer
P H
PH
Jaeger
U
U
D001483:Base Sequence; D004249:DNA Damage; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006147:Guanine / Q000378:metabolism; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D014178:Translocation, Genetic
D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D006147:Guanine