Experimental approaches to identify cellular G-quadruplex structures and functions

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作者：

MD Antonio，R Rodriguez，S Balasubramanian

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摘要：

Genomic approaches for the detection of G-quadruplex folding sequences. Cellular imaging of G-quadruplex structures. Ligand driven alkylation and tag transfer onto G-quadruplex structures. Guanine-rich nucleic acids can fold into non-canonical DNA secondary structures called G-quadruplexes. The formation of these structures can interfere with the biology that is crucial to sustain cellular homeostases and metabolism via mechanisms that include transcription, translation, splicing, telomere maintenance and DNA recombination. Thus, due to their implication in several biological processes and possible role promoting genomic instability, G-quadruplex forming sequences have emerged as potential therapeutic targets. There has been a growing interest in the development of synthetic molecules and biomolecules for sensing G-quadruplex structures in cellular DNA. In this review, we summarise and discuss recent methods developed for cellular imaging of G-quadruplexes, and the application of experimental genomic approaches to detect G-quadruplexes throughout genomic DNA. In particular, we will discuss the use of engineered small molecules and natural proteins to enable pull-down, ChIP-Seq, ChIP-chip and fluorescence imaging of G-quadruplex structures in cellular DNA.

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关键词：

G-quadruplex Genomic mapping Pull-down Cross-linking Chromatin immuno-precipitation (ChIP Cellular imaging Quinone methides DNA damage response Unbiased approaches Sequencing