5-hydroxymethylcytosine Marks Mammalian Origins Acting as a Barrier to Replication

Scientific Reports
Terezia PrikrylovaAdam B Robertson

Abstract

In most mammalian cells, DNA replication occurs once, and only once between cell divisions. Replication initiation is a highly regulated process with redundant mechanisms that prevent errant initiation events. In lower eukaryotes, replication is initiated from a defined consensus sequence, whereas a consensus sequence delineating mammalian origin of replication has not been identified. Here we show that 5-hydroxymethylcytosine (5hmC) is present at mammalian replication origins. Our data support the hypothesis that 5hmC has a role in cell cycle regulation. We show that 5hmC level is inversely proportional to proliferation; indeed, 5hmC negatively influences cell division by increasing the time a cell resides in G1. Our data suggest that 5hmC recruits replication-licensing factors, then is removed prior to or during origin firing. Later we propose that TET2, the enzyme catalyzing 5mC to 5hmC conversion, acts as barrier to rereplication. In a broader context, our results significantly advance the understating of 5hmC involvement in cell proliferation and disease states.

References

Sep 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·H TowbinJ Gordon
May 26, 1998·The EMBO Journal·S DelgadoF Antequera
Mar 11, 1999·Current Opinion in Genetics & Development·A D Donaldson, J J Blow
Aug 28, 1999·The Journal of Biological Chemistry·T ReinM L DePamphilis
Jun 29, 2000·Annual Review of Biochemistry·B K Tye
Dec 23, 2000·Science·J A WohlschlegelA Dutta
Mar 30, 2001·The Journal of Biological Chemistry·T W BurkeJ R Nevins
Jun 5, 2002·Annual Review of Biochemistry·Stephen P Bell, Anindya Dutta
Jun 13, 2002·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Hideo Nishitani, Zoi Lygerou
Apr 30, 2003·Molecular Cell·Cyrus VaziriAnindya Dutta
Jan 24, 2006·Molecular and Cellular Biology·Masayoshi IizukaM Mitchell Smith
Jan 20, 2007·Genes & Development·Yuichi J Machida, Anindya Dutta
Jun 15, 2007·Cell Division·Youngjo Kim, Edward T Kipreos
Jul 17, 2007·Annual Review of Genetics·R A Sclafani, T M Holzen
Oct 7, 2008·The Journal of Biological Chemistry·Peter M J Burgers
Oct 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jean-Charles CadoretMarie-Noëlle Prioleau
Apr 11, 2009·PLoS Genetics·Joana Sequeira-MendesMaría Gómez
Apr 18, 2009·Science·Skirmantas Kriaucionis, Nathaniel Heintz
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jun-Sub ImJoon-Kyu Lee
Nov 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Cecile EvrinChristian Speck
Feb 4, 2010·Molecular Cell·Ivar IlvesMichael R Botchan
Apr 9, 2010·Annual Review of Biochemistry·Hisao MasaiMasako Oda
Feb 2, 2011·The Journal of Biological Chemistry·Agnieszka GambusJ Julian Blow
Feb 8, 2011·Nature Structural & Molecular Biology·Celina CostasCrisanto Gutierrez
May 18, 2011·Genes & Development·Aimée M Deaton, Adrian Bird
Jun 4, 2011·Nature Protocols·Tyrone RybaDavid M Gilbert
Jun 8, 2011·The Journal of Cell Biology·Akiko KumagaiWilliam G Dunphy
Jun 28, 2011·Biochemical and Biophysical Research Communications·Julia RobertsonArne Klungland
Aug 5, 2011·Genome Research·Melvenia M MartinMirit I Aladjem
Sep 3, 2011·Cell Stem Cell·Luisa CimminoIannis Aifantis
Nov 16, 2011·Nature Reviews. Genetics·Miguel R BrancoWolf Reik

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE46111

Methods Mentioned

BETA
pull-down
flow cytometry
ChIP
immunoprecipitation
Assay
ELISA
pulldown
DIP-seq
PCR

Software Mentioned

Mascot
UCSCs
Panther
HOMER
FlowJo
bedtools
plot
ngs
R
ggplot2

Related Concepts

Related Feeds

Cardiovascular Disease & TET2

Cardiovascular diseases are the number one cause of deaths globally. Tet methylcytosine dioxygenase 2 (TET2)-mediated hematopoiesis has been implicated in accelerating heart failure. Here is the latest research on cardiovascular diseases and TET2.

Related Papers

Critical Reviews in Biochemistry and Molecular Biology
Matthew W ParkerJames M Berger
Frontiers in Bioscience : a Journal and Virtual Library
Hideo Nishitani, Zoi Lygerou
Current Drug Targets
Hiroyuki Niida, Masatoshi Kitagawa
© 2021 Meta ULC. All rights reserved