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[Preprint]. 2023 Jul 13:2023.07.12.548668. [Version 1] doi: 10.1101/2023.07.12.548668

Figure 6. Phase separation from the multivalent interactions of the CTR of XLF and XRCC4 and their role in NHEJ.

Figure 6.

(a) The summary of multivalent interactions of XLF and XRCC4 CTRs characterized in this study (pink and blue wavy lines) as well as previously characterized interactions (straight grey lines). (b) Condensates may form and enhance the assembly of NHEJ super-complexes, DNA tethering, rates of enzymatic reactions, and the recruitment of other NHEJ effectors through multivalent interactions of the IDRs, extending the proposed synaptic models obtained from single-particle cryo-EM and single molecule analysis (7, 11). This occurs when the local concentrations of XLF and X4L4 (in shadow) are above a critical concentration. DNA-PKcs: DNA-dependent protein kinase catalytic subunit, WRN: Werner syndrome protein, Pol μ: DNA polymerase μ, Pol λ: DNA polymerase λ, TdT: terminal deoxynucleotidyl transferase, APTX: aprataxin, PNKP: bifunctional polynucleotide phosphatase/kinase, TDP1: tyrosyl-DNA phosphodiesterase 1, PAXX: paralog of XRCC4 and XLF, APLF: aprataxin and PNK-like factor, CYREN: cell cycle regulator of non-homologous end joining, NONO: non-POU domain-containing octamer-binding protein, SFPQ: splicing factor, proline- and glutamine-rich, lncRNAs: long non-coding RNA (1, 4, 5).