| Autor: |
Parekh VJ; Laboratory of DNA Structure and Mutagenesis, Department of Chemistry and Applied Biological Sciences, South Dakota School of Mines and Technology, Rapid City, SD 57701, USA., Niccum BA; Department of Mathematics, Florida Institute of Technology, Melbourne, FL 32901, USA., Shah R; Department of Biological Sciences, Florida Institute of Technology, Melbourne, FL 32901, USA., Rivera MA; Department of Biological Sciences, Florida Institute of Technology, Melbourne, FL 32901, USA., Novak MJ; Department of Chemistry and Applied Biological Sciences, South Dakota School of Mines and Technology; Rapid City, SD 57701, USA., Geinguenaud F; Plateforme CNanoMat & Inserm U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, F-93017 Bobigny, France., Wien F; Synchrotron SOLEIL, 91192 Gif-sur-Yvette, France., Arluison V; Laboratoire Léon Brillouin LLB, CEA, CNRS UMR12, Université Paris Saclay, CEA Saclay, 91191 Gif-sur-Yvette, France.; Université de Paris, UFR Sciences du vivant, 35 rue Hélène Brion, 75205 Paris cedex, France., Sinden RR; Laboratory of DNA Structure and Mutagenesis, Department of Chemistry and Applied Biological Sciences, South Dakota School of Mines and Technology, Rapid City, SD 57701, USA. |
| Abstrakt: |
Certain G-rich DNA repeats can form quadruplex in bacterial chromatin that can present blocks to DNA replication and, if not properly resolved, may lead to mutations. To understand the participation of quadruplex DNA in genomic instability in Escherichia coli ( E. coli ), mutation rates were measured for quadruplex-forming DNA repeats, including (G 3 T) 4 , (G 3 T) 8 , and a RET oncogene sequence, cloned as the template or nontemplate strand. We evidence that these alternative structures strongly influence mutagenesis rates. Precisely, our results suggest that G-quadruplexes form in E. coli cells, especially during transcription when the G-rich strand can be displaced by R-loop formation. Structure formation may then facilitate replication misalignment, presumably associated with replication fork blockage, promoting genomic instability. Furthermore, our results also evidence that the nucleoid-associated protein Hfq is involved in the genetic instability associated with these sequences. Hfq binds and stabilizes G-quadruplex structure in vitro and likely in cells. Collectively, our results thus implicate quadruplexes structures and Hfq nucleoid protein in the potential for genetic change that may drive evolution or alterations of bacterial gene expression. |
