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Many transcription factors are multifunctional and also influence DNA replication. So far, their mechanism of action has remained elusive. Here we show that a DNA-binding protein could rely on the same biochemical activity that activates transcription to stimulate replication from the yeast chromosomal ARS1 origin. Unexpectedly, the ability to stimulate replication from this origin was not restricted to polymerase II transcription factors, but was a property shared by polymerase III factors. Furthermore, activation of replication did not depend on the process of transcription, but rather on the ability of DNA-binding transcription factors to remodel chromatin. The natural ARS1 activator Abf1 and the other transcription factors that stimulated replication remodeled chromatin in a very similar manner. Moreover, the presence of a histone H3 mutant that was previously shown to generally increase transcription also facilitated replication from ARS1 and partially compensated for the absence of a transcription factor. We propose that multifunctional transcription factors work by influencing the chromatin architecture at replication origins so as to generate a structure that is favorable to the initiation of replication.

RNA polymerase II and III transcription factors can stimulate DNA replication by modifying origin chromatin structures