Dr. Urbain Weyemi
NCI Center for Cancer Research
Date: September 4
Time: 12:00pm – 1:00pm
Location: Science Building 1111
My talk will be focused on the dialogue between genomic instability and redox metabolism in cancer.
My talk will be focused on the dialogue between genomic instability and redox metabolism in cancer.
• Identification of KEAP1 as a synthetic lethality metabolic partner with the DNA repair protein ATM kinase in lung cancer
• Identification of peroxiredoxin 1 (PRDX1) as a synthetic lethal partner with ATM kinase in lung cancer
• PRDX1 function: PRDX1 is a conserved thiol-dependent peroxidase that scavenges reactive oxygen species and regulates redox signaling.
• Physiological impact: PRDX1 deficiency in mice leads to genomic instability, shortened lifespan, and increased tumor development.
• Nucleolar role: Loss of PRDX1 disrupts nucleolar morphology and impairs RNA Polymerase-I-dependent transcription of pre-ribosomal RNA.
• Genome instability: PRDX1 deficiency promotes nucleolar genomic instability by stabilizing secondary DNA structures, including RNA–DNA hybrids (R-loops) and G-quadruplex DNA.
• Ribosome biogenesis: PRDX1 loss reduces nascent rRNA production and impairs rRNA processing, affecting ribosome assembly.
• DNA damage response: PRDX1 deficiency activates the nucleolar DNA damage response, including ATM activation and recruitment of TCOF1 and the MRN complex component NBS1 to rDNA loci.
• Protective mechanism: NBS1 accumulation correlates with repression of rDNA transcription, potentially protecting nucleolar DNA from further oxidative damage.
• Key conclusion: PRDX1 is a critical regulator of nucleolar integrity and ribosome biogenesis through redox-dependent control of rDNA transcription and processing.
https://ccr.cancer.gov/staff-directory/urbain-weyemi#biography