R-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instability

• DOI: 10.1038/s41467-021-27530-y
• Publication Date: 2021-12-16T11:07:13Z
• Authors: Thorsten Mosler; Francesca Conte; Gabriel M. C. Longo; Ivan Mikicic; Nastasja Kreim; Martin M. Möckel; Giuseppe Petrosino; Johanna Flach; Joan Barau; Brian Luke; Vassilis Roukos; Petra Beli
• Keywords: Transcription

Transcription poses a threat to genomic stability through the formation of R-loops that can obstruct progression replication forks. are three-stranded nucleic acid structures formed by an RNA-DNA hybrid with displaced non-template DNA strand. We developed Proximity Proteomics map R-loop proximal proteome human cells using quantitative mass spectrometry. implicate different cellular proteins in regulation and identify role tumor suppressor DDX41 opposing double strand break accumulation promoters. is enriched promoter regions vivo, unwind hybrids vitro. upon loss accompanied stress, increase breaks transcriptome changes associated inflammatory response. Germline loss-of-function mutations lead predisposition acute myeloid leukemia adulthood. propose instability-associated response may contribute development familial AML mutated DDX41.