Recruitment and activation of the PARP9-DTX3L heterodimer in response to DNA damage

• Grant number: 22/10783-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2022
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Nicolas Carlos Hoch
• Grantee: Dulce María González Duré
• 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 signalling and repair are regulated by a variety of post-translational modifications, including ubiquitination and ADP-ribosylation. We have previously identified the ADP-ribosyl transferase PARP9 and the ubiquitin ligase DTX3L in an in vitro screen for factors that bind to ADP-ribosylated Histone H2B, which is a PARP3 catalysed modification induced by DNA damage. Here, we will study the role of PARP3 in the recruitment and activation of the PARP9/DTX3L heterodimer at DNA damage sites in vivo, in order to further characterize this hitherto unknown DNA damage signalling pathway. (AU)