A simple topological filter in a eukaryotic transposon as a mechanism to suppress genome instability.
DNA transposition takes place within a higher-order complex known as the transpososome. Almost everything known about its assembly has been gleaned from bacterial transposons. Here we present a detailed analysis of transpososome assembly in the human Hsmar1 element. The transpososome is nominally symmetrical, consisting of two identical transposon ends and a dimer of transposase. However, after the transposase dimer has captured the first transposon end, an asymmetry is introduced, raising a barrier against recruitment of the second end. The barrier can be overcome by right-handed plectonemic intertwining of the transposon ends. This likely occurs mainly during transcription and episodes of nucleosome remodeling. Plectonemic intertwining favors only synapsis of closely linked transposon ends in the inverted-repeat configuration and therefore suppresses the promiscuous synapsis of distant transposon ends, which initiate McClintock's chromosomal breakage-fusion-bridge cycles in maize. We also show that synapsis of the transposon ends is a prerequisite for the first catalytic step. This provides constraints on the enzymatic mechanism of the double-strand breaks in mariner transposition, excluding the most prevalent of the current models.
School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom. chalmers@nottingham.ac.uk.
Corentin
C
Claeys Bouuaert
Danxu
D
Liu
Ronald
R
Chalmers
D002384:Catalysis; D023902:Chromosome Pairing; D004251:DNA Transposable Elements / Q000235:genetics*; D004278:DNA, Superhelical; D056890:Eukaryota / Q000235:genetics*; D042822:Genomic Instability; D006801:Humans; D009690:Nucleic Acid Conformation; D019895:Transposases / Q000235:genetics / Q000378:metabolism
D004251:DNA Transposable Elements; D004278:DNA, Superhelical; D019895:Transposases