The PARP9-DTX3L heterodimer and DNA damage-induced interferon signalling

• Grant number: 19/06769-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2019
• End date: October 31, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Nicolas Carlos Hoch
• Grantee: Maísa Moreira Gonçalves da Silva
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/18007-5 - Protein ADP-ribosylation: DNA damage signalling and impacts on human health, AP.JP

Abstract

DNA damage activates pleiotropic cellular responses such as cell cycle arrest and senescence, but can also induce an inflammatory interferon response, which is an anti-viral pathway activated by the presence of DNA in the cytoplasm. We have identified PARP9 and DTX3L, two proteins that form a heterodimer in cells and are expressed from a shared interferon-responsive promoter, in a screen for factors that bind a DNA damage-induced histone modification. Subsequently, we found that deletion of DTX3L sensitizes cells to a poorly characterized form of DNA damage. Here, we will study how PARP9 and DTX3L influence the interplay between DNA damage signalling and interferon responses.