In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 2134-2134
Abstract:
RecQ helicases contribute diverse activities towards genome maintenance in response to a variety of DNA lesions. Human RecQ homologs include RECQ1, BLM, WRN, RECQL4, and RECQ5α. Although these RecQ proteins are similar in their catalytic core and share certain biochemical properties in vitro, mutations in BLM, WRN and RecQ4 lead to clinically distinct diseases of cancer predisposition. This suggests that each human RecQ protein functions in distinct molecular events, but their specialized functions are only vaguely understood. RECQ1 is the most abundant but poorly characterized RecQ homolog in humans. Biochemically, RECQ1 displayed distinct substrate specificities from WRN and BLM, indicating that these helicases likely perform non-overlapping functions. Cellular studies imply that RECQ1 is involved in cellular proliferation and maintenance of genomic stability. We have obtained key preliminary evidence suggesting a unique role of RECQ1 in repair of oxidative DNA damage. RECQ1 is quickly recruited to the chromatin when cells are exposed to hydrogen peroxide (H2O2). Remarkably, the chromatin localization of RECQ1 is more robust and rapid than that of WRN helicase which has been shown to function in oxidative DNA damage repair. Deficiency in WRN or BLM helicase result in reduced homologous recombination and over-activation of PARP under basal condition; however, RECQ1-deficiency did not lead to PARP activation in undamaged cells and resulted in a comparatively modest, but significant, reduction in relative homologous recombination repair. In stark contrast to what is seen in WRN-deficiency, RECQ1-depleted cells over-activate PARP in a specific response to H2O2 treatment. Nonetheless, similar to WRN, RECQ1 associates with PARP-1 in human cells. Our results suggest a novel and non-overlapping role of RecQ1 in exogenously induced-oxidative DNA damage repair via modulation of PARP-1. Given that several RecQ proteins exhibit interaction with PARP-1, this study should provide a paradigm to delineate specialized and redundant functions of human RecQ homologs in DNA repair mechanisms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2134. doi:1538-7445.AM2012-2134
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-2134
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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