DNA-Directed Base Pair Opening

Strand separation is a fundamental molecular process essential for the reading of the genetic information during DNA replication, transcription and recombination. However, DNA melting in physiological conditions in which the double helix is expected to be stable represents a challenging problem. Cur...

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Main Author: Youri Timsit
Format: Article
Language:English
Published: MDPI AG 2012-10-01
Series:Molecules
Subjects:
Online Access:http://www.mdpi.com/1420-3049/17/10/11947
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author Youri Timsit
author_facet Youri Timsit
author_sort Youri Timsit
collection DOAJ
description Strand separation is a fundamental molecular process essential for the reading of the genetic information during DNA replication, transcription and recombination. However, DNA melting in physiological conditions in which the double helix is expected to be stable represents a challenging problem. Current models propose that negative supercoiling destabilizes the double helix and promotes the spontaneous, sequence-dependent DNA melting. The present review examines an alternative view and reveals how DNA compaction may trigger the sequence dependent opening of the base pairs. This analysis shows that in DNA crystals, tight DNA-DNA interactions destabilize the double helices at various degrees, from the alteration of the base-stacking to the opening of the base-pairs. The electrostatic repulsion generated by the DNA close approach of the negatively charged sugar phosphate backbones may therefore provide a potential source of the energy required for DNA melting. These observations suggest a new molecular mechanism for the initial steps of strand separation in which the coupling of the DNA tertiary and secondary interactions both actively triggers the base pair opening and stabilizes the intermediate states during the melting pathway.
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spelling doaj.art-80cb3b02566d4ec7b2c9332a542176e62022-12-21T17:57:14ZengMDPI AGMolecules1420-30492012-10-011710119471196410.3390/molecules171011947DNA-Directed Base Pair OpeningYouri TimsitStrand separation is a fundamental molecular process essential for the reading of the genetic information during DNA replication, transcription and recombination. However, DNA melting in physiological conditions in which the double helix is expected to be stable represents a challenging problem. Current models propose that negative supercoiling destabilizes the double helix and promotes the spontaneous, sequence-dependent DNA melting. The present review examines an alternative view and reveals how DNA compaction may trigger the sequence dependent opening of the base pairs. This analysis shows that in DNA crystals, tight DNA-DNA interactions destabilize the double helices at various degrees, from the alteration of the base-stacking to the opening of the base-pairs. The electrostatic repulsion generated by the DNA close approach of the negatively charged sugar phosphate backbones may therefore provide a potential source of the energy required for DNA melting. These observations suggest a new molecular mechanism for the initial steps of strand separation in which the coupling of the DNA tertiary and secondary interactions both actively triggers the base pair opening and stabilizes the intermediate states during the melting pathway.http://www.mdpi.com/1420-3049/17/10/11947DNA-meltingstrand separationDNA condensationcrystal structurebase pair openingunstackingtranscription initiation
spellingShingle Youri Timsit
DNA-Directed Base Pair Opening
Molecules
DNA-melting
strand separation
DNA condensation
crystal structure
base pair opening
unstacking
transcription initiation
title DNA-Directed Base Pair Opening
title_full DNA-Directed Base Pair Opening
title_fullStr DNA-Directed Base Pair Opening
title_full_unstemmed DNA-Directed Base Pair Opening
title_short DNA-Directed Base Pair Opening
title_sort dna directed base pair opening
topic DNA-melting
strand separation
DNA condensation
crystal structure
base pair opening
unstacking
transcription initiation
url http://www.mdpi.com/1420-3049/17/10/11947
work_keys_str_mv AT youritimsit dnadirectedbasepairopening