期刊
PARASITOLOGY
卷 140, 期 4, 页码 547-559出版社
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0031182012002028
关键词
Leishmania amazonensis; DNA double-stranded break; LaRPA-1; RAD51; telomeres
类别
资金
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, FAPESP [09/53336-0]
- Conselho Nacional de Pesquisa, CNPq [474425/2010-0]
- CNPq (Brazil)
- FAPESP (Brazil)
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [09/53336-0] Funding Source: FAPESP
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.
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