Polymerase κ Recruits DDX23 To Promote R-Loop Resolution

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Genome stability is crucial and threatened by DNA damage and R-loops.
• Translesion synthesis (TLS) pathways, including polymerase kappa (Pol κ), are vital for managing DNA lesions.
• Pol κ is known to bypass certain DNA adducts and participate in DNA repair.

Purpose of the Study:

• To identify Pol κ interacting proteins and elucidate its function in maintaining genome stability.
• To investigate the role of Pol κ in the resolution of R-loops.

Main Methods:

• Proximity labeling and affinity pull-down assays were used to identify Pol κ interactors.
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for proteomic analysis.
• Cellular localization and R-loop accumulation were assessed upon Pol κ and DDX23 manipulation.

Main Results:

• Pol κ was found to interact with DDX23.
• Pol κ localizes to R-loop sites within the chromatin.
• Pol κ recruits DDX23 to R-loop sites, facilitating R-loop resolution.
• Ablation of either Pol κ or DDX23 leads to increased R-loop accumulation.

Conclusions:

• A novel interaction between Pol κ and DDX23 was discovered.
• Pol κ and DDX23 collaborate to resolve R-loops, thereby maintaining genome stability.
• This Pol κ-DDX23 pathway is essential for preventing R-loop accumulation.