Connections between the RNAPII degradation, DNA damage response, and mRNA processing

Abstract

Eukaryotic cells have evolved multiple mechanisms to deal with DNA damage in order to prevent disease. In the presence of helix distorting DNA damage, RNA polymerase II (RNAPII) blockage at damage sites can lead to RNAPII degradation and activation of the DNA damage response (DDR), if the damage is not repaired promptly. Our hypothesis is that proteins involved in RNAPII degradation, such as Elc1, Def1 and Rpb9 in yeast, are also involved in regulating the DDR and other related cellular processes like mRNA maturation in response to DNA damage. Our data suggest that Def1 and Rpb9 could be involved in activating the DNA damage response through Rad53 (a protein involved in DNA damage signaling) while Elc1 is involved in blocking mRNA maturation after UV‐type DNA damage. We are currently exploring the role of Rpb9 and Def1 in regulating mRNA maturation following helix distorting DNA damage, using a PCR based assay. We will present these unexpected interconnections between RNAPII degradation, the DNA damage response, and mRNA processing.Support or Funding InformationKilmer Grant for AH. Presidential Scholars Funding for AH. Kilmer Grant for MS. Research Grant and Sponsorship for FN.