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

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dc.contributor.authorBrannvoll, Andre
dc.contributor.authorXue, Xiaoyu
dc.contributor.authorKwon, Youngho
dc.contributor.authorKompocholi, Smaragdi
dc.contributor.authorSimonsen, Anne Katrine W.
dc.contributor.authorViswalingam, Keerthana S.
dc.contributor.authorGonzalez, Leticia
dc.contributor.authorHickson, Ian D.
dc.contributor.authorOestergaard, Vibe H.
dc.contributor.authorMankouri, Hocine W.
dc.contributor.authorSung, Patrick
dc.contributor.authorLisby, Michael
dc.date.accessioned2020-07-15T19:58:18Z
dc.date.available2020-07-15T19:58:18Z
dc.date.issued2020-07
dc.description.abstractReplication-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.
dc.description.departmentChemistry and Biochemistry
dc.formatText
dc.format.extent25 pages
dc.format.medium1 file (.pdf)
dc.identifier.citationBrannvoll, 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).
dc.identifier.doihttps://doi.org/10.1016/j.celrep.2020.107849
dc.identifier.issn2211-1247
dc.identifier.urihttps://hdl.handle.net/10877/12092
dc.language.isoen
dc.publisherElsevier
dc.rights.holder© 2020 The Author(s).
dc.rights.licenseThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
dc.sourceCell Reports, 2020, Vol. 32, No. 1.
dc.subjectDNA helicases
dc.subjectDNA repair processes
dc.subjectZGRF1
dc.subjectChemistry and Biochemistry
dc.titleThe ZGRF1 Helicase Promotes Recombinational Repair of Replication-Blocking DNA Damage in Human Cells
dc.typeArticle

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