NDLI: Mechanisms of chromium-induced suppression of RNA synthesis in cellular and cell-free systems: Relationship to RNA polymerase arrest

Content Provider	Springer Nature Link
Author	Xu, Jian Manning, Francis C.R. O'Brien, Travis J. Ceryak, Susan Patier, Steven R.
Copyright Year	2004
Abstract	Chromium(VI) (Cr(VI)) can suppress both DNA replication and transcription as a result of chromium (Cr)-induced DNA damage. While progress has been made in the characterization of Cr-induced DNA polymerase arresting lesions, very little information is available on the inhibition of transcription by this metal. The aim of the present study was to identify the molecular mechanisms involved in the reduction of RNA synthesis by Cr. Following treatment with a moderately cytotoxic dose (~ LC$_{50}$) of Cr(VI) (150 μM for 2 h), total RNA synthesis was initially suppressed in CHO cells and recovered to control levels within 72 h post-treatment. In vitro nuclear run-on transcription assays of nuclei isolated from Cr(VI)-treated cells showed a similar amount of RNA synthesis suppression as observed in intact cells. Qualitative analysis of nascent transcripts revealed a general, concentration-dependent reduction in size suggesting that transcriptional elongation was inhibited following Cr-treatment. Transcriptional initiation in these nuclei was also reduced. To better determine whether transcriptional suppression was related to Cr-induced DNA damage we examined the transcriptional activity of T7 RNA polymerase on Cr(III)-treated plasmid DNA. Treatment of pGEM3Z-TS DNA with Cr(III) resulted in transcriptional arrest which occurred primarily at GC-rich and palindromic regions. However, in contrast to the cellular data, transcriptional initiation was unaffected in the in vitro transcription arrest assays. Taken together, these results suggest that the suppression of RNA synthesis by Cr is related to chromium-induced template DNA damage which prevents elongation leading to premature RNA polymerase arrest.
Starting Page	151
Ending Page	160
Page Count	10
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	255
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Kluwer Academic Publishers
Publisher Date	2004-01-01
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cardiology Medical Biochemistry Oncology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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