Universität zu Köln

Pokhilko, Alexandra, Zhao, Jia, Stark, W. Marshall, Colloms, Sean D. and Ebenhoeh, Oliver (2017). A simplified mathematical model of directional DNA site-specific recombination by serine integrases. J. R. Soc. Interface, 14 (126). LONDON: ROYAL SOC. ISSN 1742-5662

Full text not available from this repository.

Abstract

Serine integrases catalyse site-specific recombination to integrate and excise bacteriophage genomes into and out of their host's genome. These enzymes exhibit remarkable directionality; in the presence of the integrase alone, recombination between attP and attB DNA sites is efficient and irreversible, giving attL and attR products which do not recombine further. However, in the presence of the bacteriophage-encoded recombination directionality factor (RDF), integrase efficiently promotes recombination between attL and attR to re-form attP and attB. The DNA substrates and products of both reactions are approximately isoenergetic, and no cofactors (such as adenosine triphosphate) are required for recombination. The thermodynamic driving force for directionality of these reactions is thus enigmatic. Here, we present a minimal mathematical model which can explain the directionality and regulation of both 'forward' and 'reverse' reactions. In this model, the substrates of the 'forbidden' reactions (between attL and attR in the absence of RDF, attP and attB in the presence of RDF) are trapped as inactive protein-DNA complexes, ensuring that these 'forbidden' reactions are extremely slow. The model is in good agreement with the observed in vitro kinetics of recombination by phi C31 integrase, and defines core features of the system necessary and sufficient for directionality.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pokhilko, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhao, Jia UNSPECIFIED UNSPECIFIED UNSPECIFIED Stark, W. Marshall UNSPECIFIED UNSPECIFIED UNSPECIFIED Colloms, Sean D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ebenhoeh, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-247571
DOI:	10.1098/rsif.2016.0618
Journal or Publication Title:	J. R. Soc. Interface
Volume:	14
Number:	126
Date:	2017
Publisher:	ROYAL SOC
Place of Publication:	LONDON
ISSN:	1742-5662
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PHI-C31 INTEGRASE; MECHANISM; SYNAPSIS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24757