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ATR-dependent checkpoint modulates XPA nuclear import in response to UV irradiation

Oncogene volume 26, pages 757–764 (2007)Cite this article

Abstract

In response to DNA damage, mammalian cells activate various DNA repair pathways to remove DNA lesions and, meanwhile, halt cell cycle progressions to allow sufficient time for repair. The nucleotide excision repair (NER) and the ATR-dependent cell cycle checkpoint activation are two major cellular responses to DNA damage induced by UV irradiation. However, how these two processes are coordinated in the response is poorly understood. Here we showed that the essential NER factor XPA (xeroderma pigmentosum group A) underwent nuclear accumulation upon UV irradiation, and strikingly, such an event occurred in an ATR (Ataxia-Telangiectasia mutated and RAD3-related)-dependent manner. Either treatment of cells with ATR kinase inhibitors or transfection of cells with small interfering RNA targeting ATR compromised the UV-induced XPA nuclear translocation. Consistently, the ATR-deficient cells displayed no substantial XPA nuclear translocation while the translocation remained intact in ATM (Ataxia-Telangiectasia mutated)-deficient cells in response to UV irradiation. Moreover, we found that ATR is required for the UV-induced nuclear focus formation of XPA. Taken together, our results suggested that the ATR checkpoint pathway may modulate NER activity through the regulation of XPA redistribution in human cells upon UV irradiation.

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Acknowledgements

We thank Dr Priscilla B Wyrick for her generous assistance in immunofluorescence measurements. This study was supported by NCI Grant CA86927 (to YZ).

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  1. X Wu and S M Shell: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, James H Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA

    X Wu, S M Shell, Y Liu & Y Zou

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Correspondence to Y Zou.

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Wu, X., Shell, S., Liu, Y. et al. ATR-dependent checkpoint modulates XPA nuclear import in response to UV irradiation. Oncogene 26, 757–764 (2007). https://doi.org/10.1038/sj.onc.1209828

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