Roles of Rad51 paralogs for promoting homologous recombination in Leishmania infantum.

Abstract:

:To achieve drug resistance Leishmania parasite alters gene copy number by using its repeated sequences widely distributed through the genome. Even though homologous recombination (HR) is ascribed to maintain genome stability, this eukaryote exploits this potent mechanism driven by the Rad51 recombinase to form beneficial extrachromosomal circular amplicons. Here, we provide insights on the formation of these circular amplicons by analyzing the functions of the Rad51 paralogs. We purified three Leishmania infantum Rad51 paralogs homologs (LiRad51-3, LiRad51-4 and LiRad51-6) all of which directly interact with LiRad51. LiRad51-3, LiRad51-4 and LiRad51-6 show differences in DNA binding and annealing capacities. Moreover, it is also noteworthy that LiRad51-3 and LiRad51-4 are able to stimulate Rad51-mediated D-loop formation. In addition, we succeed to inactivate the LiRad51-4 gene and report a decrease of circular amplicons in this mutant. The LiRad51-3 gene was found to be essential for cell viability. Thus, we propose that the LiRad51 paralogs play crucial functions in extrachromosomal circular DNA amplification to circumvent drug actions and preserve survival.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Genois MM,Plourde M,Éthier C,Roy G,Poirier GG,Ouellette M,Masson JY

doi

10.1093/nar/gkv118

subject

Has Abstract

pub_date

2015-03-11 00:00:00

pages

2701-15

issue

5

eissn

0305-1048

issn

1362-4962

pii

gkv118

journal_volume

43

pub_type

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