| Full text | |
| Author(s): |
Total Authors: 3
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| Affiliation: | [1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, BR-14049900 Ribeirao Preto, SP - Brazil
Total Affiliations: 1
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| Document type: | Journal article |
| Source: | Molecular Microbiology; v. 90, n. 5, p. 1074-1087, DEC 2013. |
| Web of Science Citations: | 8 |
| Abstract | |
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) | |
| FAPESP's process: | 11/50489-0 - Characterization of the role of the nuclear protein LmHus1 in DNA damage sensing and repair in the protozoan Leishmania |
| Grantee: | Luiz Ricardo Orsini Tosi |
| Support Opportunities: | Regular Research Grants |