Publication Date:
2014-03-29
Description:
In bacterial cells, processing of double-stranded DNA breaks for repair by homologous recombination is dependent upon the recombination hotspot sequence chi (Chi) and is catalysed by either an AddAB- or RecBCD-type helicase-nuclease (reviewed in refs 3, 4). These enzyme complexes unwind and digest the DNA duplex from the broken end until they encounter a chi sequence, whereupon they produce a 3' single-stranded DNA tail onto which they initiate loading of the RecA protein. Consequently, regulation of the AddAB/RecBCD complex by chi is a key control point in DNA repair and other processes involving genetic recombination. Here we report crystal structures of Bacillus subtilis AddAB in complex with different chi-containing DNA substrates either with or without a non-hydrolysable ATP analogue. Comparison of these structures suggests a mechanism for DNA translocation and unwinding, suggests how the enzyme binds specifically to chi sequences, and explains how chi recognition leads to the arrest of AddAB (and RecBCD) translocation that is observed in single-molecule experiments.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991583/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991583/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krajewski, Wojciech W -- Fu, Xin -- Wilkinson, Martin -- Cronin, Nora B -- Dillingham, Mark S -- Wigley, Dale B -- 100401/Wellcome Trust/United Kingdom -- 12799/Cancer Research UK/United Kingdom -- A12799/Cancer Research UK/United Kingdom -- Cancer Research UK/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2014 Apr 17;508(7496):416-9. doi: 10.1038/nature13037. Epub 2014 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Division of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK [2] CRT Discovery Laboratories, Department of Biological Sciences, Birkbeck, University of London, London WC1E 7HX, UK. ; Division of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK. ; School of Biochemistry, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670664" target="_blank"〉PubMed〈/a〉
Keywords:
Adenosine Triphosphate/analogs & derivatives/metabolism
;
Bacillus subtilis/*enzymology
;
Bacterial Proteins/*chemistry/*metabolism
;
Binding Sites
;
Crystallography, X-Ray
;
DNA/chemistry/genetics/metabolism
;
DNA Helicases/*chemistry/metabolism
;
Exodeoxyribonucleases/*chemistry/*metabolism
;
Models, Molecular
;
Molecular Conformation
;
Recombination, Genetic/*genetics
;
Structure-Activity Relationship
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
