Document Detail


Competition between the RNA transcript and the nontemplate DNA strand during R-loop formation in vitro: a nick can serve as a strong R-loop initiation site.
MedLine Citation:
PMID:  19841062     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Upon transcription of some sequences by RNA polymerases in vitro or in vivo, the RNA transcript can thread back onto the template DNA strand, resulting in an R loop. Previously, we showed that initiation of R-loop formation at an R-loop initiation zone (RIZ) is favored by G clusters. Here, using a purified in vitro system with T7 RNA polymerase, we show that increased distance between the promoter and the R-loop-supporting G-rich region reduces R-loop formation. When the G-rich portion of the RNA transcript is downstream from the 5' end of the transcript, the ability of this portion of the transcript to anneal to the template DNA strand is reduced. When we nucleolytically resect the beginning of the transcript, R-loop formation increases because the G-rich portion of the RNA is now closer to the 5' end of the transcript. Short G-clustered regions can act as RIZs and reduce the distance-induced suppression of R-loop formation. Supercoiled DNA is known to favor transient separation of the two DNA strands, and we find that this favors R-loop formation even in non-G-rich regions. Most strikingly, a nick can serve as a strong RIZ, even in regions with no G richness. This has important implications for class switch recombination and somatic hypermutation and possibly for other biological processes in transcribed regions.
Authors:
Deepankar Roy; Zheng Zhang; Zhengfei Lu; Chih-Lin Hsieh; Michael R Lieber
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  30     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-16     Completed Date:  2010-01-14     Revised Date:  2010-09-28    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  146-59     Citation Subset:  IM    
Affiliation:
Department of Pathology, USC Norris Comprehensive Cancer Center, Los Angeles, CA 90089-9176, USA.
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MeSH Terms
Descriptor/Qualifier:
5' Flanking Region
DNA / chemistry,  genetics*
DNA Breaks, Single-Stranded*
DNA, Superhelical / chemistry,  genetics
DNA-Directed RNA Polymerases / chemistry
RNA / chemistry,  genetics*
Templates, Genetic
Transcription Initiation Site
Transcription, Genetic*
Viral Proteins / chemistry
Chemical
Reg. No./Substance:
0/DNA, Superhelical; 0/Viral Proteins; 63231-63-0/RNA; 9007-49-2/DNA; EC 2.7.7.-/bacteriophage T7 RNA polymerase; EC 2.7.7.6/DNA-Directed RNA Polymerases
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