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 brea k repair. Previously, we detected two mammalian nuclear proteins of 100 and 75 kDa (POMp100 and POMp75, respectively) that are able to promote homolog ous DNA pairing, a key step in homologous recombination. Here me describe t he identification of human (h) POMp75 as the pro-oncoprotein TLS/FUS, hPOMp 75/TLS binds both single- and double-stranded DNAs and mediates annealing o f complementary DNA strands. More important, it promotes the uptake of a si ngle-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 cat alyzed by hPOMp75/TLS require Mg2+ and are ATP-independent. Interestingly, the oncogenic fusion form TLS-CHOP is not able to promote DNA pairing. Thes e data suggest a possible role for hPOMp75/TLS in maintenance of genomic in tegrity.