A5023752637- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
University of South Florida
2016-2023
Timely stalling and resumption of RNA polymerases at damaged chromatin are actively regulated processes. Prior work showed an importance FACT histone chaperone in such process. Here we provide a new role OTUD5 deubiquitinase the FACT-dependent Through DUB RNAi screen, found as specific stabilizer UBR5 E3 ligase. localizes to DNA double strand breaks (DSBs), interacts with represses Pol II elongation synthesis. co-localizes component SPT16 antagonizes H2A deposition DSB lesions. independently...
Significance The BMI1-containing Polycomb Repressive Complex is an important gene silencer during development, stem cell maintenance, and cancer progression. BMI1 also involved in DNA damage response, but its downstream mechanism unclear. Here we identified UBR5 as a factor whose chromatin recruitment regulated by BMI1. We showed that repress the RNA polymerase II (Pol II) elongation nascent synthesis at UV-induced lesions. associates with regulates abundance of histone chaperon complex FACT...
Common fragile sites (CFSs) are breakage-prone genomic loci, and considered to be hotspots for rearrangements frequently observed in cancers. Understanding the underlying mechanisms CFS instability will lead better insight on cancer etiology. Here we show that Polycomb group proteins BMI1 RNF2 suppressors of transcription-replication conflicts (TRCs) instability. Cells depleted or showed slower replication forks elevated fork stalling. These phenotypes associated with increase occupancy RNA...
Abstract Proper regulation of replication fork progression is important for genomic maintenance. Subverting the transcription-induced conflicts crucial in preserving integrity forks. Various chromatin remodelers, such as histone chaperone and deacetylases are known to modulate stress, but how these factors organized or collaborate not well understood. Here we found a new role OTUD5 deubiquitinase limiting stress. We that recruited forks, its depletion causes Through C-terminal disordered...
Abstract Common fragile sites (CFSs) are breakage-prone genomic loci, and considered to be hotspots for rearrangements frequently observed in cancers. Understanding the underlying mechanisms CFS instability will lead better insight on cancer etiology. Here we show that Polycomb group proteins BMI1 RNF2 suppressors of transcription-replication conflicts (TRCs) instability. Cells depleted or showed slower replication forks elevated fork stalling. These phenotypes associated with increase...