Human POMp75 is identified as the pro-oncoprotein TLS/FUS: both POMp75 andPOMp100 DNA homologous pairing activities are associated to cell proliferation

We have previously developed an assay to measure DNA homologous pairing act ivities in crude extracts: The POM blot. In mammalian nuclear extracts, we detected two major DNA homologous pairing activities: POMp100 and POMp75. H ere, we present the purification and identification of POMp75 as the pro-on coprotein TLS/FUS. Because of the pro-oncogene status of TLS/FUS, we studie d in addition, the relationships between cell proliferation and POM activit ies. We show that transformation of human fibroblasts by SV40 large T antig en results in a strong increase of both POMp100 and TLS/POMp75 activities. Although detectable levels of both POMp100 and TLS/POMp75 are observed in n on-immortalized fibroblasts or lymphocytes, fibroblasts at mid confluence o r lymphocytes stimulated by phytohaemaglutinin, show higher levels of POM a ctivities. Moreover, induction of differentiation of mouse F9 line by retin oic acid leads to the inhibition of both POMp100 and TLS/POMp75 activities. Comparison of POM activity of TLS/FUS with the amount of TLS protein detec ted by Western blot, suggests that the POM activity could be regulated by p ost-translation modification. Taken together, these results indicate that P OMp100 and TLS/POMp75 activitites are present in normal cells but are conne cted to cell proliferation. Possible relationship between cell proliferatio n, response to DNA damage and DNA homologous pairing activity of the pro-on coprotein TLS/FUS are discussed.