LmHus1 is required for the DNA damage response in Leishmania major and forms a complex with an unusual Rad9 homologue

Autor(es)

Damasceno, Jeziel D. ^[1] ; Nunes, Vinicius S. ^[1] ; Tosi, Luiz R. O. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular Microbiology; v. 90, n. 5, p. 1074-1087, DEC 2013.
• Citações Web of Science: 8

Resumo

Genotoxic stress activates checkpoint-signalling pathways leading to cell cycle arrest and DNA repair. In many eukaryotes, the Rad9-Hus1-Rad1 (9-1-1) checkpoint complex participates in the early steps of the DNA damage response to replicative stress and is a pivotal contributor to genome homeostasis. The remarkable genome plasticity of the protozoan Leishmania hints at a peculiar DNA metabolism in these ancient eukaryotes. Therefore, we set out to investigate the existence of homologues of the 9-1-1 components in Leishmania major and found that LmHus1 and LmRad9 are phylogenetically related to the 9-1-1 complex subunits from other eukaryotes. Altered levels of LmHus1 and LmRad9 affected the parasite ability to manage genotoxic stress and LmHus1-defficent cells were defective in controlling cell cycle progression in response to genotoxic stress. Upon DNA damage, LmHus1 was recruited to the chromatin and colocalized with the single-stranded DNA-binding protein LmRpa1. Also, LmHus1 interacted with LmRad9 to form a DNA damage responsive complex in vivo. Altogether, our data strongly indicate the participation of LmHus1, LmRad9 and LmRpa1 in the L.majorDNA damage response and suggest their involvement in genome maintenance mechanisms. (AU)

• Processo FAPESP: 11/50489-0 - Caracterização do papel da proteína nuclear LmHus1 em mecanismos de detecção e reparo de danos no DNA do protozoário Leishmania
• Beneficiário: Luiz Ricardo Orsini Tosi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 07/54504-9 - Estudo da associação da proteína LmHus1 a extremidades cromossômicas de Leishmania major
• Beneficiário: Jeziel Dener Damasceno
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 07/55728-8 - Caracterizacao do gene lmhus1 e de sua participacao no fenomeno de amplificacao genica em leishmania spp.
• Beneficiário: Vinícius Santana Nunes
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 04/08868-0 - Consolidação do Centro de Microscopia Funcional do Campus da USP/ Ribeirão Preto
• Beneficiário: Roy Edward Larson
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários