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SUMMARY:External Seminar "Hot in front! Hunting host replication by integr
 ating ahead of replication forks during replicative DNA transposition" by 
 Bernard Hallet
DTSTART:20251210T100000Z
DTEND:20251210T113000Z
DTSTAMP:20260909T034400Z
UID:indico-event-232@indico.i2bc.paris-saclay.fr
DESCRIPTION:Speakers: Francois-Xavier BARRE\n\nBernard HALLET\, UCLouvain\
 nTitle: "Hot in front! Hunting host replication by integrating ahead of re
 plication forks during replicative DNA transposition"\nAbstract: Bacteria
 l transposons of the Tn3 family are known for their prevalence in the diss
 emination of antimicrobial resistance among pathogens. The efficiency of t
 hese transposons relies on their replicative mode of transposition\, gener
 ating a new copy of themselves every time they move. Our recent work on th
 e Tn3-family transposon Tn4430 has provided new insights into how the tran
 sposition complex assembles and activates to catalyse DNA breakage and re-
 joining reactions. This include high-resolution CryoEM structures of the t
 ransposases bound to the DNA substrates at different stages of transpositi
 on. However\, the mechanism by which host DNA replication is recruited dur
 ing transposition remains unknown.Transposition of Tn4430 only occurs in t
 arget DNA molecules that undergo replication\, suggesting that ongoing tar
 get replication is crucial for replisome recruitment. Furthermore\, a geno
 me-wide analysis of Tn4430 insertion sites revealed that integration occur
 s preferentially in regions where replication dynamics is altered. In the 
 chromosome\, this corresponds to the terminus region where replisomes are 
 stalled by Tus/ter complexes\, or to regions where converging replication 
 forks meet and collide. Strong integration hotspots are also observed at o
 ther replication roadblocks\, such as head-on collisions between DNA and R
 NA polymerases downstream of highly transcribed genes. Interestingly\, the
 se hotspots overlap with the preferred binding regions of GapR\, a Cauloba
 cter crecentus protein that specifically binds to positively supercoiled D
 NA. Consistently\, alignment of Tn4430 integration sites reveals a signatu
 re sequence composed of a 7-bp 5'-CTNNNAG-3' core consensus flanked by per
 iodically alternating G/C- and A/T-rich stretches. This sequence is predic
 ted to adopt a right-handed superhelical twist such as is found at the ape
 x of positive supercoils. Together\, these results support the hypothesis
  of a replication hijacking mechanism by which Tn3-family transposons spec
 ifically integrate into transient positive DNA supercoils that form downst
 ream of replication forks\, in order to recruit the host replication machi
 nery during transposition.\n\nhttps://indico.i2bc.paris-saclay.fr/event/23
 2/
LOCATION:B24-N2-315 (I2BC CNRS Gif)
URL:https://indico.i2bc.paris-saclay.fr/event/232/
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