The mechanism of DNA replication termination in vertebrates

Nature
James M DewarJohannes C Walter

Abstract

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.

References

Apr 15, 1978·Journal of Molecular Biology·D P Tapper, M L DePamphilis
Jun 14, 1970·Journal of Molecular Biology·A J LevineF E Billheimer
May 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·S DiNardoR Sternglanz
Aug 30, 1996·The Journal of Biological Chemistry·H Hiasa, K J Marians
Jul 14, 1998·Molecular Cell·J WalterJ Newport
Apr 25, 2000·Nucleic Acids Research·D SantamaríaJ B Schvartzman
Nov 15, 2001·The EMBO Journal·I LucasO Hyrien
Jan 22, 2003·Molecular Cell·Olivier EspeliKenneth J Marians
Sep 19, 2003·The Journal of Biological Chemistry·Daniel L KaplanMike O'Donnell
Nov 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Tatyana A ProkhorovaJohannes C Walter
Jun 27, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stephen E MoyerMichael R Botchan
Nov 15, 2007·Journal of Molecular Biology·Daniel M CzajkowskyZhifeng Shao
Dec 7, 2007·Current Opinion in Cell Biology·Sara S HookAnindya Dutta
Jun 24, 2008·Molecular Cell·Jonathan Baxter, John F X Diffley
Sep 23, 2008·Cell·Markus RäschleJohannes C Walter
Dec 23, 2008·Virology·Ellen Fanning, Kun Zhao
Jul 1, 2009·Methods in Molecular Biology·Ronald LebofskyJohannes C Walter
Feb 4, 2010·Molecular Cell·Ivar IlvesMichael R Botchan
Dec 15, 2010·Molecular Cell·Hasan YardimciJohannes C Walter
Mar 8, 2011·Nature Structural & Molecular Biology·Alessandro CostaJames M Berger
Jul 2, 2011·Science·David T LongJohannes C Walter
Apr 5, 2012·Proceedings of the National Academy of Sciences of the United States of America·Young-Hoon KangJerard Hurwitz
Sep 11, 2012·Nature Methods·Anna B LovelandAntoine M van Oijen
Apr 9, 2013·Molecular Cell·Sean R McGuffeeIestyn Whitehouse
Jul 31, 2013·Nature·Christian J RudolphRobert G Lloyd
Jul 31, 2013·Nature Chemical Biology·Paola MagnaghiAntonella Isacchi
Sep 26, 2013·Nucleic Acids Research·Adrian CharbinFrank Uhlmann
Sep 16, 2014·Molecular Cell·David T LongJohannes C Walter
Oct 11, 2014·Cell·Julien P DuxinJohannes C Walter
Oct 25, 2014·Science·Sara Priego MorenoAgnieszka Gambus
Feb 3, 2015·Nature Structural & Molecular Biology·Jieqiong ZhangJohannes C Walter
Jun 14, 2015·The EMBO Journal·Magda BudzowskaJohannes C Walter

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Citations

Feb 2, 2016·Journal of Molecular Biology·Ferdos Abid Ali, Alessandro Costa
Feb 13, 2016·Current Opinion in Structural Biology·Tom D Deegan, John F X Diffley
Apr 3, 2016·Nucleic Acids Research·Jakub WiktorCees Dekker
Apr 15, 2016·Nature Reviews. Molecular Cell Biology·Frank Uhlmann
May 21, 2016·Frontiers in Genetics·André FranzThorsten Hoppe
Sep 27, 2016·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Emilio Lecona, Oscar Fernandez-Capetillo
Jan 18, 2017·Genesis : the Journal of Genetics and Development·Erica RaspelliVincenzo Costanzo
Dec 24, 2016·Genes·Andrea KeszthelyiJonathan Baxter
Jan 18, 2017·Critical Reviews in Biochemistry and Molecular Biology·Matthew W ParkerJames M Berger
Mar 9, 2017·Genes & Development·David Akopian, Michael Rape
Apr 28, 2017·Nature Cell Biology·Vincent Gaggioli, Philip Zegerman
Dec 7, 2017·Genes & Development·Ainhoa Mariezcurrena, Frank Uhlmann
Sep 21, 2016·Molecular and Cellular Biology·George FullbrightDavid T Long
May 18, 2018·Cold Spring Harbor Protocols·Justin Sparks, Johannes C Walter
Nov 16, 2019·Cellular and Molecular Life Sciences : CMLS·Lu LiuHuiqiang Lou
Apr 12, 2020·The Journal of Biological Chemistry·Anna H Bizard, Ian D Hickson
Sep 7, 2019·Nature Communications·Zhi-Xiong ZhouThomas A Kunkel
Jun 4, 2020·Biochemical Society Transactions·Sara Priego Moreno, Agnieszka Gambus
Sep 5, 2020·Critical Reviews in Biochemistry and Molecular Biology·Thomas A Guilliam, Joseph T P Yeeles
Apr 14, 2019·Life Science Alliance·Yilin WangJason A Stewart
Jun 15, 2019·FEBS Letters·Kohji Hizume, Hiroyuki Araki
May 1, 2020·Frontiers in Microbiology·Aisha H SyedaChristian J Rudolph
Oct 1, 2020·Cancers·Agustina P BertolinVanesa Gottifredi
Sep 14, 2016·The Journal of Biological Chemistry·Kathleen M MulvaneyMichael B Major
Mar 8, 2019·Nature·R Alex WuJohannes C Walter
Nov 17, 2019·The Journal of Biological Chemistry·John K Barrows, David T Long
Jul 8, 2016·Genetics·Stephen P Bell, Karim Labib
Apr 14, 2019·Life Science Alliance·Sara Priego MorenoAgnieszka Gambus
May 26, 2017·Nature Reviews. Molecular Cell Biology·James M Dewar, Johannes C Walter
Aug 14, 2020·Genes·Alice FinardiRosella Visintin
Nov 2, 2019·Genes·Joyce H Lee, James M Berger
Sep 19, 2020·Genes & Development·Emily LowJohannes C Walter
Dec 2, 2020·Open Biology·Patricia Pérez-ArnaizThorsten Allers
Dec 22, 2020·The Journal of Cell Biology·Riko IshimotoMasatoshi Fujita
Dec 16, 2020·Trends in Cell Biology·R Alex WuJohannes C Walter

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Methods Mentioned

BETA
electrophoresis
ImmunoPrecipitation
ChIP
PCR
immunodepletion
pull-down
pull down
pull-downs

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