Genotoxic Stress Globally Downregulates Transcription in Budding Yeast

Abstract

DNA damage response significantly affects transcription. UV exposure of mammalian cells elicits global transcriptional shutdown orchestrated by an essentially enigmatic mechanism. We show here that a brief treatment of budding yeast with hydroxyurea, 4‐nitroquinoline 1‐oxide, or bleocin causes significant reduction in newly synthesized RNAs produced by all three RNA polymerases. This effect is not restricted to S phase and is suppressed by inactivation of checkpoint kinases MEC1 and RAD53, as well as by inactivation of histone chaperones ASF1 and RTT106. In addition, the genotoxic stress leads to removal of TATA‐binding protein from promoters of genes transcribed by all three RNA polymerases and removal of RNA Pol I and RNA Pol II from the corresponding genes. The effect of genotoxic stress on the stability of preinitiation complexes (PICs) does not seem to be significantly suppressed by ASF1, RAD53, or MEC1 inactivation. Together, our data suggest that genotoxic stress affects stability of PICs and production of new RNAs by at least partly independent mechanisms.