Human DNA helicase HELQ participates in DNA interstrand crosslink tolerance with ATR and RAD51 paralogs

Kei-ichi Takata, Shelley Reh, Junya Tomida, Maria D. Person and Richard D. Wood ()
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Kei-ichi Takata: The University of Texas MD Anderson Cancer Center Science Park
Shelley Reh: The University of Texas MD Anderson Cancer Center Science Park
Junya Tomida: The University of Texas MD Anderson Cancer Center Science Park
Maria D. Person: ICMB Protein and Metabolite Analysis Facility, University of Texas at Austin
Richard D. Wood: The University of Texas MD Anderson Cancer Center Science Park

Nature Communications, 2013, vol. 4, issue 1, 1-11

Abstract: Abstract Mammalian HELQ is a 3′–5′ DNA helicase with strand displacement activity. Here we show that HELQ participates in a pathway of resistance to DNA interstrand crosslinks (ICLs). Genetic disruption of HELQ in human cells enhances cellular sensitivity and chromosome radial formation by the ICL-inducing agent mitomycin C (MMC). A significant fraction of MMC sensitivity is independent of the Fanconi anaemia pathway. Sister chromatid exchange frequency and sensitivity to UV radiation or topoisomerase inhibitors is unaltered. Proteomic analysis reveals that HELQ is associated with the RAD51 paralogs RAD51B/C/D and XRCC2, and with the DNA damage-responsive kinase ATR. After treatment with MMC, reduced phosphorylation of the ATR substrate CHK1 occurs in HELQ-knockout cells, and accumulation of G2/M cells is reduced. The results indicate that HELQ operates in an arm of DNA repair and signalling in response to ICL. Further, the association with RAD51 paralogs suggests HELQ as a candidate ovarian cancer gene.

Date: 2013
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DOI: 10.1038/ncomms3338

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