Leishmania replication protein A-1 binds in vivo single-stranded telomeric DNA

Siqueira-Neto, Jair L.; Lira, Cristina B.B.; Giardini, Miriam A.; Khater, Letícia; Perez, Ana Paula da Silva; Peroni, L; Reis, José Raimundo Ribeiro dos; Freitas‐Junior, Lúcio H.; Ramos, Carlos H.I.; Cano, Maria Isabel Nogueira

doi:10.1016/j.bbrc.2007.04.144

Cited by 33 publications

(49 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The 9‐1‐1/RPA interaction involves both the carboxy‐terminus of Rad9 and the RPA70N domain of the Rpa1 subunit (http://onlinelibrary.wiley.com/doi/10.1111/mmi.12418/suppinfo) (Xu et al ., ). The putative L. major LmRpa1 (ORF LmjF.28.1820) has a predicted molecular mass of 51 KDa, similar to its Leishmania amazonensis orthologue LaRpa1 (Neto et al ., ). LmRpa1 is smaller than its human homologue (HsRpa1), whose molecular mass is ∼ 70 KDa.…”

Section: Resultsmentioning

confidence: 97%

LmHus1 is required for the DNA damage response in Leishmania major and forms a complex with an unusual Rad9 homologue

Damasceno

Nunes

Tosi

2013

Molecular Microbiology

View full text Add to dashboard Cite

SummaryGenotoxic stress activates checkpoint-signalling pathways leading to cell cycle arrest and DNA repair. In many eukaryotes, the Rad9-Hus1-Rad1 (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 Leishmania 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 Leishmania major and found that LmHus1 and LmRad9 are phylogenetically related to the 9-1-1 complex subunits from other eukaryotes. Altered levels of LmHus1 and LmRad9 affected the parasite ability to manage genotoxic stress and LmHus1-defficent cells were defective in controlling cell cycle progression in response to genotoxic stress. Upon DNA damage, LmHus1 was recruited to the chromatin and colocalized with the single-stranded DNAbinding protein LmRpa1. Also, LmHus1 interacted with LmRad9 to form a DNA damage responsive complex in vivo. Altogether, our data strongly indicate the participation of LmHus1, LmRad9 and LmRpa1 in the L. major DNA damage response and suggest their involvement in genome maintenance mechanisms.

show abstract

Section: Resultsmentioning

confidence: 97%

LmHus1 is required for the DNA damage response in Leishmania major and forms a complex with an unusual Rad9 homologue

Damasceno

Nunes

Tosi

2013

Molecular Microbiology

View full text Add to dashboard Cite

show abstract

“…; Neto et al. ), we first investigated the presence of TcRPA‐1 at T. cruzi telomeres by ChIP and FISH‐IF assays. Anti‐TcRPA‐1 was able to immunoprecipitate telomeric DNA, while preimmune serum was not (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…; Neto et al. ), earlier‐divergent eukaryotes, RPA is associated with chromosomal extremities. If the investigation of these ancient organisms allows us to see through the evolution, it is time to raise the possibility that RPA and telomeres are indeed old partners.…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Replication Protein A‐1 Has a Preference for the Telomeric G‐rich Sequence in Trypanosoma cruzi

Pavani

Vitarelli

Fernandes

et al. 2017

J Eukaryotic Microbiology

View full text Add to dashboard Cite

Replication protein A (RPA), the major eukaryotic single-stranded binding protein, is a heterotrimeric complex formed by RPA-1, RPA-2, and RPA-3. RPA is a fundamental player in replication, repair, recombination, and checkpoint signaling. In addition, increasing evidences have been adding functions to RPA in telomere maintenance, such as interaction with telomerase to facilitate its activity and also involvement in telomere capping in some conditions. Trypanosoma cruzi, the etiological agent of Chagas disease is a protozoa parasite that appears early in the evolution of eukaryotes. Recently, we have showed that T. cruziRPA presents canonical functions being involved with DNA replication and DNA damage response. Here, we found by FISH/IF assays that T. cruziRPA localizes at telomeres even outside replication (S) phase. In vitro analysis showed that one telomeric repeat is sufficient to bind RPA-1. Telomeric DNA induces different secondary structural modifications on RPA-1 in comparison with other types of DNA. In addition, RPA-1 presents a higher affinity for telomeric sequence compared to randomic sequence, suggesting that RPA may play specific roles in T. cruzi telomeric region.

show abstract

“…The contribution of DNA recombination-mediated events to VSG switching was also shown, where the same VSG expression site remains active but expresses a different VSG (reviewed in (9,14–18)). Two telomeric double-stranded DNA binding proteins, TbRAP1 and TbTRF, were shown to colocalize with T. brucei telomeres (19,20), and two Leishmania amazonensis proteins, LaRbp38 and LaRPA-1, were shown to bind telomeric DNA (21,22). Interestingly, LaRbp38 also localizes to the kinetoplast, the single mitochondrion of trypanosomatids (21).…”

Section: Introductionmentioning

confidence: 99%

Trypanosoma brucei UMSBP2 is a single-stranded telomeric DNA binding protein essential for chromosome end protection

Klebanov-Akopyan¹,

Mishra²,

Glousker

et al. 2018

Nucleic Acids Research

View full text Add to dashboard Cite

Universal minicircle sequence binding proteins (UMSBPs) are CCHC-type zinc-finger proteins that bind a single-stranded G-rich sequence, UMS, conserved at the replication origins of the mitochondrial (kinetoplast) DNA of trypanosomatids. Here, we report that Trypanosoma brucei TbUMSBP2, which has been previously proposed to function in the replication and segregation of the mitochondrial DNA, colocalizes with telomeres at the nucleus and is essential for their structure, protection and function. Knockdown of TbUMSBP2 resulted in telomere clustering in one or few foci, phosphorylation of histone H2A at the vicinity of the telomeres, impaired nuclear division, endoreduplication and cell growth arrest. Furthermore, TbUMSBP2 depletion caused rapid reduction in the G-rich telomeric overhang, and an increase in C-rich single-stranded telomeric DNA and in extrachromosomal telomeric circles. These results indicate that TbUMSBP2 is essential for the integrity and function of telomeres. The sequence similarity between the mitochondrial UMS and the telomeric overhang and the finding that UMSBPs bind both sequences suggest a common origin and/or function of these interactions in the replication and maintenance of the genomes in the two organelles. This feature could have converged or preserved during the evolution of the nuclear and mitochondrial genomes from their ancestral (likely circular) genome in early diverged protists.

show abstract

Leishmania replication protein A-1 binds in vivo single-stranded telomeric DNA

Cited by 33 publications

References 32 publications

LmHus1 is required for the DNA damage response in Leishmania major and forms a complex with an unusual Rad9 homologue

LmHus1 is required for the DNA damage response in Leishmania major and forms a complex with an unusual Rad9 homologue

Replication Protein A‐1 Has a Preference for the Telomeric G‐rich Sequence in Trypanosoma cruzi

Trypanosoma brucei UMSBP2 is a single-stranded telomeric DNA binding protein essential for chromosome end protection

Contact Info

Product

Resources

About