The epistatic relationship of Drosophila melanogaster CtIP and Rif1 in homology-directed repair of DNA double-strand breaks.

Autor:	Thomas MS; Department of Human Science, School of Health, Georgetown University Medical Center, Washington, D.C. 20057, USA., Pillai GS; Department of Human Science, School of Health, Georgetown University Medical Center, Washington, D.C. 20057, USA., Butler MA; Department of Human Science, School of Health, Georgetown University Medical Center, Washington, D.C. 20057, USA., Fernandez J; Department of Human Science, School of Health, Georgetown University Medical Center, Washington, D.C. 20057, USA., LaRocque JR; Department of Human Science, School of Health, Georgetown University Medical Center, Washington, D.C. 20057, USA.
Jazyk:	angličtina
Zdroj:	G3 (Bethesda, Md.) [G3 (Bethesda)] 2024 Nov 06; Vol. 14 (11).
DOI:	10.1093/g3journal/jkae210
Abstrakt:	Double-strand breaks (DSBs) are genotoxic DNA lesions that pose significant threats to genomic stability, necessitating precise and efficient repair mechanisms to prevent cell death or mutations. DSBs are repaired through nonhomologous end-joining (NHEJ) or homology-directed repair (HDR), which includes homologous recombination (HR) and single-strand annealing (SSA). CtIP and Rif1 are conserved proteins implicated in DSB repair pathway choice, possibly through redundant roles in promoting DNA end-resection required for HDR. Although the roles of these proteins have been well-established in other organisms, the role of Rif1 and its potential redundancies with CtIP in Drosophila melanogaster remain elusive. To examine the roles of DmCtIP and DmRif1 in DSB repair, this study employed the direct repeat of white (DR-white) assay, tracking across indels by decomposition (TIDE) analysis, and P{wIw_2 kb 3'} assay to track repair outcomes in HR, NHEJ, and SSA, respectively. These experiments were performed in DmCtIPΔ/Δ single mutants, DmRif1Δ/Δ single mutants, and DmRif1Δ/Δ; DmCtIPΔ/Δ double mutants. This work demonstrates significant defects in both HR and SSA repair in DmCtIPΔ/Δ and DmRif1Δ/Δ single mutants. However, experiments in DmRif1Δ/Δ; DmCtIPΔ/Δ double mutants reveal that DmCtIP is epistatic to DmRif1 in promoting HDR. Overall, this study concludes that DmRif1 and DmCtIP do not perform their activities in a redundant pathway, but rather DmCtIP is the main driver in promoting HR and SSA, most likely through its role in end resection. Competing Interests: Conflicts of interest No authors have any conflicts of interest to declare. (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)
Databáze:	MEDLINE
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