Publications by authors named "A K Bielinsky"
RAD18 is a conserved eukaryotic E3 ubiquitin ligase that promotes genome stability through multiple pathways. One of these is gap-filling DNA synthesis at active replication forks and in post-replicative DNA. RAD18 also regulates homologous recombination (HR) repair of DNA breaks; however, the current literature describing the contribution of RAD18 to HR in mammalian systems has not reached a consensus.
View Article and Find Full Text PDFHomologous recombination (HR) and translesion synthesis (TLS) promote gap-filling DNA synthesis to complete genome replication. One factor involved in both pathways is RAD18, an E3 ubiquitin ligase. Although RAD18's role in promoting TLS through the ubiquitination of PCNA at lysine 164 (K164) is well established, its requirement for HR-based mechanisms is currently less clear.
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- Innovative methods for isolating proteins linked to DNA replication have revealed insights into how DNA replication forks stall.
- A technique called iPOND2-DRIPPER enhances the retrieval and quantification of replication proteins, increasing their levels by up to 300 times compared to standard controls.
- This approach also allows for the direct observation of ubiquitination events and the recruitment of DNA repair factors when replication is stalled, highlighting interactions with nuclear structures.
Article Synopsis
- Eukaryotic genome stability relies on various molecular processes, including the action of STUbLs (SUMO-targeted E3 ligases) that support DNA repair and replication.
- This study investigates the role of the human STUbL RNF4 in cancer cells lacking MCM10, highlighting its importance in preventing G-phase accumulation and promoting DNA synthesis under replication stress.
- Findings indicate that RNF4 and MCM10 function differently in humans compared to yeast, with RNF4 helping to avoid severe DNA under-replication when MCM10 is deficient, ultimately ensuring cell viability.
Article Synopsis
- - The study presents a cost-effective chemical-genetic screening platform that focuses on DNA damage response by using a custom sgRNA library targeting 1011 genes.
- - It demonstrated that the new approach successfully identified chemical-genetic interactions (CGIs) that matched expected outcomes, and achieved a signal-to-noise ratio similar to traditional genome-wide screens.
- - Additionally, the time-resolved screening revealed a previously unidentified pathway for repairing DNA damage caused by camptothecin, providing valuable insights while using significantly fewer resources.