期刊
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
卷 743, 期 -, 页码 89-96出版社
ELSEVIER
DOI: 10.1016/j.mrfmmm.2012.12.002
关键词
BLM helicase; DNA topoisomerase I; rRNA transcription; Bloom's syndrome; Nucleolus; RNA polymerase I
资金
- National Institutes of Health [CA117898]
- Ohio State University Pelotonia Fellowship Program
- Ohio State University Medical Scientist Training Program (MSTP)
- National Center For Advancing Translational Sciences [8UL1TR000090-05, 8KL2TR000112-05, 8TL1TR000091-05]
Bloom's syndrome (BS) is an inherited disorder caused by loss of function of the recQ-like BLM helicase. It is characterized clinically by severe growth retardation and cancer predisposition. BLM localizes to PML nuclear bodies and to the nucleolus; its deficiency results in increased intra- and inter-chromosomal recombination, including hyper-recombination of rDNA repeats. Our previous work has shown that BLM facilitates RNA polymerase I-mediated rRNA transcription in the nucleolus (Grierson et al., 2012 [18]). This study uses protein co-immunoprecipitation and in vitro transcription/translation (IVTT) to identify a direct interaction of DNA topoisomerase I with the C-terminus of BLM in the nucleolus. In vitro helicase assays demonstrate that DNA topoisomerase I stimulates BLM helicase activity on a nucleolar-relevant RNA:DNA hybrid, but has an insignificant effect on BLM helicase activity on a control DNA:DNA duplex substrate. Reciprocally, BLM enhances the DNA relaxation activity of DNA topoisomerase I on super-coiled DNA substrates. Our study suggests that BLM and DNA topoisomerase I function coordinately to modulate RNA:DNA hybrid formation as well as relaxation of DNA supercoils in the context of nucleolar transcription. (C) 2012 Elsevier B.V. All rights reserved.
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