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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The natural absence of RPA1N domain did not impair Leishmania amazonensis RPA-1 participation in DNA damage response and telomere protection

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Author(s):
Viveiros Da Silveira, Rita De Cassia [1] ; Da Silva, Marcelo Santos [1] ; Nunes, Vinicius Santana [1] ; Perez, Arina Marina [1] ; Nogueira Cano, Maria Isabel [1]
Total Authors: 5
Affiliation:
[1] Univ Estadual Paulista Julio Mesquita Filho UNESP, Inst Biociencias, Dept Genet, BR-18618970 Botucatu, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Parasitology; v. 140, n. 4, p. 547-559, APR 2013.
Web of Science Citations: 9
Abstract

We have previously shown that the subunit 1 of Leishmania amazonensis RPA (LaRPA-1) alone binds the G-rich telomeric strand and is structurally different from other RPA-1. It is analogous to telomere end-binding proteins described in model eukaryotes whose homologues were not identified in the protozoan's genome. Here we show that LaRPA-1 is involved with damage response and telomere protection although it lacks the RPA1N domain involved with the binding with multiple checkpoint proteins. We induced DNA double-strand breaks (DSBs) in Leishmania using phleomycin. Damage was confirmed by TUNEL-positive nuclei and triggered a G1/S cell cycle arrest that was accompanied by nuclear accumulation of LaRPA-1 and RAD51 in the S phase of hydroxyurea-synchronized parasites. DSBs also increased the levels of RAD51 in non-synchronized parasites and of LaRPA-1 and RAD51 in the S phase of synchronized cells. More LaRPA-1 appeared immunoprecipitating telomeres in vivo and associated in a complex containing RAD51, although this interaction needs more investigation. RAD51 apparently co-localized with few telomeric clusters but it did not immunoprecipitate telomeric DNA. These findings suggest that LaRPA-1 and RAD51 work together in response to DNA DSBs and at telomeres, upon damage, LaRPA-1 works probably to prevent loss of single-stranded DNA and to assume a capping function. (AU)

FAPESP's process: 09/53336-0 - Project title, identification of possible interactions among the DNA repair machinery and telomere maintenance in Leishmania spp.
Grantee:Maria Isabel Nogueira Cano
Support Opportunities: Regular Research Grants