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LmHus 1 is required for the DNA damage response in L eishmania major and forms a complex with an unusual Rad 9 homologue
Author(s) -
Damasceno Jeziel D.,
Nunes Vinicius S.,
Tosi Luiz R. O.
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12418
Subject(s) - biology , dna damage , chromatin , g2 m dna damage checkpoint , cell cycle checkpoint , dna repair , dna , microbiology and biotechnology , genome , genome instability , chek1 , genetics , cell cycle , cell , gene
Summary Genotoxic stress activates checkpoint‐signalling pathways leading to cell cycle arrest and DNA repair. In many eukaryotes, the Rad 9– Hus 1– Rad 1 (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 L eishmania 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 L eishmania major and found that LmHus 1 and LmRad 9 are phylogenetically related to the 9‐1‐1 complex subunits from other eukaryotes. Altered levels of LmHus 1 and LmRad 9 affected the parasite ability to manage genotoxic stress and LmHus 1‐defficent cells were defective in controlling cell cycle progression in response to genotoxic stress. Upon DNA damage, LmHus 1 was recruited to the chromatin and colocalized with the single‐stranded DNA ‐binding protein LmRpa 1. Also, LmHus 1 interacted with LmRad 9 to form a DNA damage responsive complex in vivo . Altogether, our data strongly indicate the participation of LmHus 1, LmRad 9 and LmRpa 1 in the L. major DNA damage response and suggest their involvement in genome maintenance mechanisms.