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

Autor(es)

Nunes, Vinicius Santana ^{[1, 2]} ; Moretti, Nilmar Silvio ^[1] ; da Silva, Marcelo Santos ^[3] ; Elias, Maria Carolina ^[3] ; Janzen, Christian J. ^[4] ; Schenkman, Sergio ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04032039 Sao Paulo, SP - Brazil

^[2] Hosp Evangel Vila Velha, Ctr Ensino Pesquisa & Inovaccio, BR-29118060 Vila Velha, ES - Brazil

^[3] Inst Butantan, Lab Especial Ciclo Celular, Sao Paulo, SP - Brazil

^[4] Univ Wurzburg, Dept Cell & Dev Biol, Bioctr, D-97074 Wurzburg - Germany

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH; v. 1867, n. 7 JUL 2020.
• Citações Web of Science: 0

Resumo

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.H2A 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 of cytokinesis. (AU)

• Processo FAPESP: 14/03714-7 - Interação da proteína Sir2 com fatores de início de tradução em Trypanosoma
• Beneficiário: Vinícius Santana Nunes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado