New evidence of an ability to recognize homologous genes as an intrinsic property encoded into DNA structure

Homologous recombination can accurately repair DNA double strand breaks that might otherwise be fatal. It can also combine parts of chromosomes from two parents into one single chromosome, allowing viable offspring to be genetically different from both parents.

HFSP Program Grant holder Alexei Kornyshev and colleagues
authored on Tue, 26 July 2016

Homologous recombination requires that regions of two different double stranded DNAs align with matching sequences in registration, so that the two dsDNAs can be combined into one.  It is not yet known how these genes can rapidly and correctly align in vivo even though there are millions of possible incorrect alignments. Several local and global mechanisms for pairing homologous sequences in vitro were proposed, and several experiments performed indicating that the ability to recognize sequence homology may be a property intrinsic to the structure of DNA. 

This new in vitro study by a collaboration between Harvard University and Imperial College London reports and monitors reversible homologous pairing within one long double-stranded DNA molecule containing two long homologous sequences oriented head-to head. Pairing is observed by measuring the end-to-end distance of the molecule which decreases if these sequences pair forming a DNA loop. Results show that the pairing can be reversed by applying a force that pulls the paired regions apart, thereby unfolding the loop. For many single molecules, multiple reversible pairing cycles were observed even though no proteins were present. This decisive evidence may inspire new in vivo experiments studying protein free mechanisms for establishing homologous pairing.

Link to the full story from Imperial College London


Evidence of protein-free homology recognition in magnetic bead force–extension experiments. Lee DJ(O’), Danilowicz C, Rochester C, Kornyshev AA, Prentiss M. Proc. R. Soc. A Published 20 July 2016.DOI: 10.1098/rspa.2016.0186.

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