The ZGRF1 Helicase Promotes Recombinational Repair of Replication-Blocking DNA Damage in Human Cells




Brannvoll, Andre
Xue, Xiaoyu
Kwon, Youngho
Kompocholi, Smaragdi
Simonsen, Anne Katrine W.
Viswalingam, Keerthana S.
Gonzalez, Leticia
Hickson, Ian D.
Oestergaard, Vibe H.
Mankouri, Hocine W.

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Replication-blocking DNA lesions are particularly toxic to proliferating cells because they can lead to chromosome missegregation if not repaired prior to mitosis. In this study, we report that ZGRF1 null cells accumulate chromosome aberrations following replication perturbation and show sensitivity to two potent replication-blocking anticancer drugs: mitomycin C and camptothecin. Moreover, ZGRF1 null cells are defective in catalyzing DNA damage-induced sister chromatid exchange despite accumulating excessive FANCD2, RAD51, and γ-H2AX foci upon induction of interstr and DNA crosslinks. Consistent with a direct role in promoting recombinational DNA repair, we show that ZGRF1 is a 5'-to-3' helicase that catalyzes D-loop dissociation and Holliday junction branch migration. Moreover, ZGRF1 physically interacts with RAD51 and stimulates strand exchange catalyzed by RAD51-RAD54. On the basis of these data, we propose that ZGRF1 promotes repair of replication-blocking DNA lesions through stimulation of homologous recombination.



DNA helicases, DNA repair processes, ZGRF1, Chemistry and Biochemistry


Brannvoll, A., Xue, X., Kwon, Y., Kompocholi, S., Simonsen, A. K. W., Viswalingam, K. S., Gonzalez, L., Hickson, I. D., Oestergaard, V. H., Mankouri, H. W., Sung, P., & Lisby, M.(2020). The ZGRF1 helicase promotes recombinational repair of replication-blocking DNA damage in human cells. Cell Reports, 32(1).


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