Trimethylation of histone H3K76 by Dot1B enhances cell cycle progression after mitosis in Trypanosoma cruzi

Biochimica Et Biophysica Acta. Molecular Cell Research
Vinicius Santana NunesSergio Schenkman

Abstract

Dot1 enzymes are histone methyltransferases that mono-, di- and trimethylate lysine 79 of histone H3 to affect several nuclear processes. The functions of these different methylation states are still largely unknown. Trypanosomes, which are flagellated protozoa that cause several parasitic diseases, have two Dot1 homologues. Dot1A catalyzes the mono- and dimethylation of lysine 76 during late G2 and mitosis, and Dot1B catalyzes trimethylation, which is a modification found in all stages of the cell cycle. Here, we generated Trypanosoma cruzi lines lacking Dot1B. Deletion of one allele resulted in parasites with increased levels of mono- and dimethylation and a reduction in H3K76me3. In the full knockout (DKO), no trimethylation was observed. Both the DKO and the single knockout (SKO) showed aberrant morphology and decreased growth due to cell cycle arrest after G2. This phenotype could be rescued by caffeine in the DKO, as caffeine is a checkpoint inhibitor of the cell cycle. The knockouts also phosphorylated γH2A without producing extensive DNA breaks, and Dot1B-depleted cells were more susceptible to general checkpoint kinase inhibitors, suggesting that a lack of H3K76 trimethylation prevents the initiation and/or completion ...Continue Reading

References

May 1, 1995·Molecular and Biochemical Parasitology·M I CanoJ L Ramirez
May 29, 2000·Molecular and Cellular Biology·B A MoserP Russell
May 30, 2002·Molecular and Biochemical Parasitology·María I SantoriMaría T Téllez-Iñón
Jun 28, 2002·Cell·Fred van LeeuwenDaniel E Gottschling
Jan 6, 2004·Journal of Protein Chemistry·Maritza CalabokisJosé Bubis
Nov 5, 2004·Nature·Yentram HuyenThanos D Halazonetis
Sep 17, 2005·Molecular and Cellular Biology·Robert WysockiStephen J Kron
Jan 27, 2006·The Journal of Biological Chemistry·Xiaoming TuChing C Wang
Jul 11, 2006·BMC Biotechnology·Martin C Taylor, John M Kelly
Dec 23, 2006·Protist·Maria Carolina EliasSergio Schenkman
Jul 1, 2008·Molecular and Biochemical Parasitology·Sam Alsford, David Horn
Jul 4, 2008·PLoS Biology·Luisa M FigueiredoGeorge A M Cross
Feb 21, 2009·Environmental and Molecular Mutagenesis·Michelle Barbi de MouraCarlos Renato Machado
Jul 5, 2011·Genes & Development·Anh Tram Nguyen, Yi Zhang
Jul 16, 2011·EMBO Reports·Dirk De VosFred van Leeuwen
Feb 23, 2012·Molecular and Biochemical Parasitology·Lucy Glover, David Horn
Sep 4, 2012·Nucleic Acids Research·Alwine GassenChristian J Janzen
May 3, 2013·Open Biology·Bungo Akiyoshi, Keith Gull
May 18, 2013·Cell Division·Guillaume ChouinardEstelle Schmitt
Nov 30, 2013·Trends in Parasitology·Calvin TiengweRichard McCulloch
Mar 7, 2014·Microbiology and Molecular Biology Reviews : MMBR·Marie-Michelle GenoisJean-Yves Masson
Apr 1, 2014·Molecular and Biochemical Parasitology·Simone CalderanoM Carolina Elias
Nov 19, 2014·Journal of Molecular Cell Biology·Laura ZanniniGiacomo Buscemi
Feb 19, 2015·Nucleic Acids Research·Simone Guedes CalderanoMaria Carolina Elias
Feb 26, 2015·Nucleic Acids Research·Valentina Turinetto, Claudia Giachino
Dec 29, 2015·Parasitology International·María Agostina Di RenzoMariana Potenza
Mar 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Qing ZhouZiyin Li

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