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2015 ; 525
(7569
): 345-50
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The mechanism of DNA replication termination in vertebrates
#MMPMID26322582
Dewar JM
; Budzowska M
; Walter JC
Nature
2015[Sep]; 525
(7569
): 345-50
PMID26322582
show ga
Eukaryotic DNA replication terminates when replisomes from adjacent replication
origins converge. Termination involves local completion of DNA synthesis,
decatenation of daughter molecules and replisome disassembly. Termination has
been difficult to study because termination events are generally asynchronous and
sequence nonspecific. To overcome these challenges, we paused converging
replisomes with a site-specific barrier in Xenopus egg extracts. Upon removal of
the barrier, forks underwent synchronous and site-specific termination, allowing
mechanistic dissection of this process. We show that DNA synthesis does not slow
detectably as forks approach each other, and that leading strands pass each other
unhindered before undergoing ligation to downstream lagging strands. Dissociation
of the replicative CMG helicase (comprising CDC45, MCM2-7 and GINS) occurs only
after the final ligation step, and is not required for completion of DNA
synthesis, strongly suggesting that converging CMGs pass one another and
dissociate from double-stranded DNA. This termination mechanism allows rapid
completion of DNA synthesis while avoiding premature replisome disassembly.
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