Polymerase κ Recruits DDX23 To Promote R‑Loop Resolution

Genome stability is constantly threatened by DNA damage
and noncanonical
nucleic acid structures, e.g., R-loops. Translesion synthesis (TLS)
constitutes a major pathway for cells to cope with unrepaired DNA
lesions. In this vein, polymerase κ (Pol κ) was shown
to maintain genome stability by promoting error-free bypass of minor-groove N2-modified 2′-deoxyguanosine adducts
and by participating in DNA repair. To explore functions of Pol κ,
we employed two independent approaches, proximity labeling and affinity
pull-down, followed by liquid chromatography–tandem mass spectrometry
(LC-MS/MS) analysis, to profile the Pol κ-interaction proteome.
We found that Pol κ interacts with DDX23 and the polymerase
is enriched at R-loop loci in chromatin. In addition, Pol κ
recruits DDX23 to R-loop sites to promote DDX23-mediated R-loop resolution,
where individual ablation of Pol κ and DDX23 led to augmented
accumulation of R-loops in cells. Together, we discovered an interaction
between Pol κ and DDX23 and revealed the functions of this interaction
in R-loop resolution.