RECQ1 expression is upregulated in response to DNA damage and in a p53-dependent manner

Parvathaneni, Swetha, Lu, Xing, Choudhary, Ritu, Lal, Ashish, Madhusudan, Srinivasan and Sharma, Sudha (2017) RECQ1 expression is upregulated in response to DNA damage and in a p53-dependent manner. Oncotarget . ISSN 1949-2553

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Sensitivity of cancer cells to DNA damaging chemotherapeutics is determined by DNA repair processes. Consequently, cancer cells may upregulate the expression of certain DNA repair genes as a mechanism to promote chemoresistance. Here, we report that RECQ1, a breast cancer susceptibility gene that encodes the most abundant RecQ helicase in humans, is a p53-regulated gene, potentially acting as a defense against DNA damaging agents. We show that RECQ1 mRNA and protein levels are upregulated upon treatment of cancer cells with a variety of DNA damaging agents including the DNA-alkylating agent methylmethanesulfonate (MMS). The MMS-induced upregulation of RECQ1 expression is p53-dependent as it was observed in p53-proficient but not in isogenic p53-deficient cells. The RECQ1 promoter is bound by endogenous p53 and is responsive to p53 in luciferase reporter assays suggesting that RECQ1 is a direct target of p53. Treatment with the chemotherapeutic drugs temozolomide and fotemustine also increased RECQ1 mRNA levels whereas depletion of RECQ1 enhanced cellular sensitivity to these agents. These results identify a previously unrecognized p53-mediated upregulation of RECQ1 expression in response to DNA damage and implicate RECQ1 in the repair of DNA lesions including those induced by alkylating and other chemotherapeutic agents.

Item Type: Article
Keywords: RecQ, Helicase, DNA damage, p53, Gene expression
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Cancer and Stem Cells
Identification Number:
Depositing User: Madhusudan, Srinivasan
Date Deposited: 26 May 2017 12:47
Last Modified: 04 May 2020 18:46

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