WRN helicase accelerates the transcription of ribosomal RNA as a component of an RNA polymerase I-associated complex

Shiratori, Miwa; Suzuki, Takahisa; Itoh, Chie; Goto, Makoto; Furuichi, Yasuhiro; Matsumoto, Takehisa

doi:10.1038/sj.onc.1205334

Cited by 79 publications

(72 citation statements)

References 47 publications

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“…Both mRNA and rRNA synthesis are indeed downregulated in cells from WS patients. 36,37 The exonuclease and unwinding activity of the WRN helicase can also act upon RNA-DNA heteroduplexes, which may explain its role in transcription and subsequent cell proliferation and survival. 38 A defect in overall RNA levels and synthesis in WS fibroblasts may not be rescued by hTERT, despite the ability of hTERT to extent the replication capacity of WS cells.…”

Section: Why Do Cells That Lack Wrn Senesce In Response To Myc?mentioning

confidence: 99%

Functional Link Between Myc and the Werner Gene in Tumorigenesis

Grandori¹,

Robinson²,

Galloway³

et al. 2004

Cell Cycle

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Section: Why Do Cells That Lack Wrn Senesce In Response To Myc?mentioning

confidence: 99%

Functional Link Between Myc and the Werner Gene in Tumorigenesis

Grandori¹,

Robinson²,

Galloway³

et al. 2004

Cell Cycle

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“…The detailed procedure was described previously. 21) RESULTS Genotoxic Effect of E2 and BPA DNA damage in MCF-7 cells was assessed by measuring the CTL. E2 was added at concentrations from 10 Ϫ9 to 10 Ϫ7 M, which induced Comet formation after 3 h, after which the CTL increased dose dependently (Table 1).…”

Section: Chemicalsmentioning

confidence: 99%

DNA Damage Caused by Bisphenol A and Estradiol through Estrogenic Activity

Iso

Watanabe

Iwamoto

et al. 2006

Biological & Pharmaceutical Bulletin

Self Cite

149

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Epidemiological studies and animal experiments have shown carcinogenic properties of estrogen. Studies to clarify the molecular mechanisms of carcinogenesis by estrogen suggest that estrogen causes carcinogenic effects by combined genotoxicity and stimulation of cell proliferation. [1][2][3] Estrogen causes DNA damage by estrogen-derived oxidants, 4,5) DNA adducts formed by estrogen metabolites 5,6) and formation of micronuclei. 7,8) Recent studies strongly suggest that DNA damage induced by estrogen is dependent on estrogen receptors (ER): the ER antagonist tamoxifen inhibits E2 effects in ER-positive MCF-7 cells, but not in ERnegative MDA-MB-231 cells. 4,9) Detoxifying enzyme activity markedly decreases by treatment with 17b-estradiol (E2) in MCF-7 cells, leading to increased susceptibility of cells to DNA damage, but E2 has no effect on detoxifying enzyme activity in MDA-MB-231 cells. 4)Bisphenol A (BPA) was first shown to be estrogenic in 1938 in ovariectomized rats 10) and later in MCF-7 human breast cancer cell culture assay. 11) BPA is an endocrine-disrupting chemical and has a weak affinity for ER, estimated at about 1/1000 of E2, 12) and its additional estrogenic effects on the hormonal homeostatic system has recently received much attention.We also studied proteins involved in the repair of DNA damage induced by E2 and BPA. Histone H2AX (H2AFX) is responsible for maintaining genomic stability by recognizing DNA double-strand breaks.13) At the sites of stalled replication forks, H2AX is phosphorylated to gH2AX, which forms foci 14) that appear immediately after DNA damage and recruit proteins responsible for repair of DNA damage, including Bloom helicase (BLM), 14,15) the product of BLM that is the causative gene of Bloom syndrome, an autosomal recessive genetic disorder. 16,17) Clinical features of patients having Bloom syndrome include growth retardation, immunodeficiency, male infertility but not female infertility, and a high incidence of cancers. Cells from Bloom syndrome patients show a high frequency of sister chromatid exchange. 18,19) BLM responds to DNA damage and accumulates at the site of DNA double-strand breaks and physically interacts with gH2AX.15) In this study we investigated the effects of E2 and BPA on DNA damage in ER-positive MCF-7 and ER-negative MDA-MB-231 cells, both of which are derived from adenocarcinomas; these effects were assessed by alkaline single cell electrophoresis (Comet assay). We also investigated colocalization of gH2AX and BLM at sites of DNA damage. Science and Technology, Japan Science and Technology Agency; Kawaguchi Center Building, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan: and c Department of Urology, St Marianna University School of Medicine; 2-16-1 Sugao, Miyamae, Kawasaki 216-8511, Japan. Received September 15, 2005; accepted November 15, 2005 Evidence exists that raises concern about genotoxic effects induced by estrogen: oxidative stress caused by estrogen-derived oxidants, DNA adducts formed by estrogen metabolites and estrogen-induce...

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“…Moreover, Laine et al (3) have shown that WRN stimulates topoisomerase I DNA-unwinding activity that could influence cellular transcription. The yeast WRN homologue, SGS1, also participates in DNA replication and RNA pol I-dependent transcription (4), and the WRN helicase enhances RNA pol I-dependent transcription of ribosomal RNA (5).…”

mentioning

confidence: 99%

The Werner Syndrome Helicase Is a Cofactor for HIV-1 Long Terminal Repeat Transactivation and Retroviral Replication

Sharma

Awasthi

Harrod

et al. 2007

Journal of Biological Chemistry

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(1) have demonstrated that WRN contributes to general RNA pol II 4 -dependent transcription, although its mechanism remains unclear. Interestingly, these authors found that a 27-amino acid direct-repeat sequence strongly activated transcription in yeast two-hybrid experiments, independent of WRN 3Ј 3 5Ј DNA helicase activity (1) (Fig. 1A) suggesting that WRN interacts with cellular factors to modulate RNA pol II-dependent transcription. The WRN protein localizes to nucleoli and the nucleoplasm of transcriptionally active cells (1, 2). Moreover, Laine et al. (3) have shown that WRN stimulates topoisomerase I DNA-unwinding activity that could influence cellular transcription. The yeast WRN homologue, SGS1, also participates in DNA replication and RNA pol I-dependent transcription (4), and the WRN helicase enhances RNA pol I-dependent transcription of ribosomal RNA (5).In the present study, we have investigated whether WRN contributes to HIV-1 LTR transactivation and retroviral replication. The HIV-1 LTR contains upstream enhancer elements (e.g. NF-B and SP1) that synergize with the transactivator protein, Tat, bound to TAR-RNA, to promote retroviral gene expression in HIV-1-infected tissues, macrophages/monocytes, and CD4 ϩ T-lymphocytes (6 -17). The mechanism by which Tat/TAR-RNA complexes regulate transcription from the HIV-1 LTR involves the concerted recruitment of a plethora of cellular factors, including p300/CREB-binding protein (p300/CBP) (18 -25), [26][27][28][29][30], P-TEFb (30 -33), SET7/SET9 methyltransferases (34), SIRT1 (35), the Brm component of the SWI/SNF chromatin-remodeling com-

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WRN helicase accelerates the transcription of ribosomal RNA as a component of an RNA polymerase I-associated complex

Cited by 79 publications

References 47 publications

Functional Link Between Myc and the Werner Gene in Tumorigenesis

Functional Link Between Myc and the Werner Gene in Tumorigenesis

DNA Damage Caused by Bisphenol A and Estradiol through Estrogenic Activity

The Werner Syndrome Helicase Is a Cofactor for HIV-1 Long Terminal Repeat Transactivation and Retroviral Replication

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