Trypanosoma brucei MRE11 is non-essential but influences growth, homologous recombination and DNA double-strand break repair.

Abstract:

:MRE11 is a conserved multi-functional protein that is important for maintaining genomic integrity in yeast and mammalian cells. By database searching, we identified a full-length candidate MRE11 on Trypanosoma brucei chromosome II. We subsequently cloned and sequenced the corresponding gene from the Lister 427 strain. MRE11 is a single copy gene that encodes an 83 kDa protein of 763 amino acids. GFP-MRE11 and Ty1-MRE11 fusion proteins localized to the nucleus of bloodstream and procyclic T. brucei. Interestingly, Ty1-MRE11 associated, to some extent, with telomeres of procyclic but not bloodstream forms. This association appears cell-cycle dependent, with the highest co-localization in G1 cells. We were able to generate an MRE11 null mutant in bloodstream forms, indicating that it is non-essential. However, the null mutant was impaired in homologous recombination, as evidenced by the reduced integration efficiency of transfected DNA. A conditional null mutant, containing a tetracycline-inducible ectopic Ty1-MRE11, exhibited reduced growth and plating efficiency and increased sensitivity to DNA double-strand breaks, induced by methyl methanesulphonate or ionizing radiation, in the absence of tetracycline.

journal_name

Mol Biochem Parasitol

authors

Tan KS,Leal ST,Cross GA

doi

10.1016/s0166-6851(02)00165-2

subject

Has Abstract

pub_date

2002-11-01 00:00:00

pages

11-21

issue

1-2

eissn

0166-6851

issn

1872-9428

pii

S0166685102001652

journal_volume

125

pub_type

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