Determinants of R-loop formation at convergent bidirectionally transcribed trinucleotide repeats

Reddy, Kaalak, Tam, Mandy, Bowater, Richard P. ORCID:, Barber, Miriam, Tomlinson, Matthew, Nichol Edamura, Kerrie, Wang, Yuh-Hwa and Pearson, Christopher E. (2011) Determinants of R-loop formation at convergent bidirectionally transcribed trinucleotide repeats. Nucleic Acids Research, 39 (5). pp. 1749-1762. ISSN 0305-1048

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R-loops have been described at immunoglobulin class switch sequences, prokaryotic and mitochondrial replication origins, and disease-associated (CAG)n and (GAA)n trinucleotide repeats. The determinants of trinucleotide R-loop formation are unclear. Trinucleotide repeat expansions cause diseases including DM1 (CTG)n, SCA1 (CAG)n, FRAXA (CGG)n, FRAXE (CCG)n and FRDA (GAA)n. Bidirectional convergent transcription across these disease repeats can occur. We find R-loops formed when CTG or CGG and their complementary strands CAG or CCG were transcribed; GAA transcription, but not TTC, yielded R-loops. R-loop formation was sensitive to DNA supercoiling, repeat length, insensitive to repeat interruptions, and formed by extension of RNA:DNA hybrids in the RNA polymerase. R-loops arose by transcription in one direction followed by transcription in the opposite direction, and during simultaneous convergent bidirectional transcription of the same repeat forming double R-loop structures. Since each transcribed disease repeat formed R-loops suggests they may have biological functions.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Science > Research Groups > Molecular Microbiology
Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry
Faculty of Science > Research Groups > Biosciences Teaching and Education Research
Depositing User: Users 2731 not found.
Date Deposited: 15 Apr 2011 11:27
Last Modified: 02 Nov 2023 01:48
DOI: 10.1093/nar/gkq935


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