Human 75-kDa DNA-pairing protein is identical to the pro-oncoprotein TLS/FUS and is able to promote D-loop formation.
Homologous recombination plays a fundamental role in DNA double-strand break repair. Previously, we detected two mammalian nuclear proteins of 100 and 75 kDa (POMp100 and POMp75, respectively) that are able to promote homologous DNA pairing, a key step in homologous recombination. Here we describe the identification of human (h) POMp75 as the pro-oncoprotein TLS/FUS. hPOMp75/TLS binds both single- and double-stranded DNAs and mediates annealing of complementary DNA strands. More important, it promotes the uptake of a single-stranded oligonucleotide into a homologous superhelical DNA to form a D-loop. The formation of a D-loop is an essential step in DNA double-strand break repair through recombination. DNA annealing and D-loop formation catalyzed by hPOMp75/TLS require Mg(2+) and are ATP-independent. Interestingly, the oncogenic fusion form TLS-CHOP is not able to promote DNA pairing. These data suggest a possible role for hPOMp75/TLS in maintenance of genomic integrity.
Baechtold
H
H
Basel Institute for Immunology, Grenzacherstrasse 487, CH-4005 Basel, Switzerland.
Kuroda
M
M
Sok
J
J
Ron
D
D
Lopez
B S
BS
Akhmedov
A T
AT
D020029:Base Pairing; D001667:Binding, Competitive; D022762:CCAAT-Enhancer-Binding Proteins; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006367:HeLa Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D034702:RNA-Binding Protein FUS; D012261:Ribonucleoproteins / Q000378:metabolism*; D051742:Transcription Factor CHOP
D022762:CCAAT-Enhancer-Binding Proteins; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D034702:RNA-Binding Protein FUS; D012261:Ribonucleoproteins; C106030:TLS-CHOP fusion protein, human; D051742:Transcription Factor CHOP; D004247:DNA