The Hop2 and Mnd1 proteins act in concert with Rad51 and Dmc1 in meiotic recombination

Petukhova, Galina V.; Pezza, Roberto J.; Vanevski, Filip; Ploquin, Mickaël J.-Y.; Masson, Jean‐Yves; Camerini‐Otero, R. Daniel

doi:10.1038/nsmb923

Cited by 162 publications

(250 citation statements)

References 33 publications

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“…3C. The order of expression of trypanosome HMGs derived here-MND1 followed by DMC1, followed by HOP1-agrees with the sequence of events in other eukaryotes (21,22,30). Cell fusion, usually involving haploids, is an integral part of mating in most eukaryotes.…”

Section: Resultsmentioning

confidence: 59%

“…The three YFP::HMGs exhibited a similar pattern of expression, with strong fluorescence only in the nuclei of morphologically distinct, dividing epimastigotes present in the SGs. The temporal order of expression of the three HMGs followed that seen in other eukaryotes and concurred with the functional roles of these proteins during meiosis (21,22). MND1 was expressed first, and HOP1 was expressed last.…”

Section: Discussionmentioning

confidence: 81%

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Identification of the meiotic life cycle stage of Trypanosoma brucei in the tsetse fly

Peacock

Ferris

Sharma

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

128

156

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Elucidating the mechanism of genetic exchange is fundamental for understanding how genes for such traits as virulence, disease phenotype, and drug resistance are transferred between pathogen strains. Genetic exchange occurs in the parasitic protists Trypanosoma brucei , T. cruzi , and Leishmania major , but the precise cellular mechanisms are unknown, because the process has not been observed directly. Here we exploit the identification of homologs of meiotic genes in the T. brucei genome and demonstrate that three functionally distinct, meiosis-specific proteins are expressed in the nucleus of a single specific cell type, defining a previously undescribed developmental stage occurring within the tsetse fly salivary gland. Expression occurs in clonal and mixed infections, indicating that the meiotic program is an intrinsic but hitherto cryptic part of the developmental cycle of trypanosomes. In experimental crosses, expression of meiosis-specific proteins usually occurred before cell fusion. This is evidence of conventional meiotic division in an excavate protist, and the functional conservation of the meiotic machinery in these divergent organisms underlines the ubiquity and basal evolution of meiosis in eukaryotes.

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Section: Resultsmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 81%

Identification of the meiotic life cycle stage of Trypanosoma brucei in the tsetse fly

Peacock

Ferris

Sharma

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

128

156

View full text Add to dashboard Cite

show abstract

“…Human RAD51 K133R, RPA, and HOP2-MND1 complex were purified according to previously published protocols (22,23). Wild type and mutant forms of Srs2 were expressed in E. coli and purified as described (24,25).…”

Section: Methodsmentioning

confidence: 99%

A Variant of the Breast Cancer Type 2 Susceptibility Protein (BRC) Repeat Is Essential for the RECQL5 Helicase to Interact with RAD51 Recombinase for Genome Stabilization

Islam

Paquet

Fox

et al. 2012

Journal of Biological Chemistry

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Background:The BRC repeat is essential for BRCA2 to bind RAD51 and promote homologous recombination. Results: A BRC repeat variant is essential for RECQL5 to bind RAD51 and suppress homologous recombination. Conclusion: The BRC repeat can be utilized to either promote or suppress homologous recombination. Significance: Discovery of multiple functions of the BRC repeat is important for understanding regulation of homologous recombination.

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“…Proteins and DNA-Human RAD51, DMC1, RAD54, RPA, BLM, BLM K695R, murine Hop2/Mnd1, and yeast Rad51 and Rad54 proteins were purified as described (38). The BLM K695A ATPase mutant was kindly provided by P. Sung.…”

Section: Methodsmentioning

confidence: 99%

Bloom Syndrome Helicase Stimulates RAD51 DNA Strand Exchange Activity through a Novel Mechanism

Bugreev

Mazina

Mazin

2009

Journal of Biological Chemistry

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Loss or inactivation of BLM, a helicase of the RecQ family, causes Bloom syndrome, a genetic disorder with a strong predisposition to cancer. Although the precise function of BLM remains unknown, genetic data has implicated BLM in the process of genetic recombination and DNA repair. Previously, we demonstrated that BLM can disrupt the RAD51-singlestranded DNA filament that promotes the initial steps of homologous recombination. However, this disruption occurs only if RAD51 is present in an inactive ADP-bound form. Here, we investigate interactions of BLM with the active ATP-bound form of the RAD51-single-stranded DNA filament. Surprisingly, we found that BLM stimulates DNA strand exchange activity of RAD51. In contrast to the helicase activity of BLM, this stimulation does not require ATP hydrolysis. These data suggest a novel BLM function that is stimulation of the RAD51 DNA pairing. Our results demonstrate the important role of the RAD51 nucleoprotein filament conformation in stimulation of DNA pairing by BLM.Mutations of BLM helicase cause Bloom syndrome (BS), 2 a rare autosomal disorder, which is associated with stunted growth, facial sun sensitivity, immunodeficiency, fertility defects, and a greatly elevated incidence of many types of cancer occurring at an early age (1). BLM belongs to the highly conserved family of RecQ helicases that are required for the maintenance of genome integrity in all organisms (2, 3). There are five RecQ helicases in humans; mutations in three of them, WRN, RECQ4, and BLM, have been associated with the genetic abnormalities known as Werner, Rothmund-Thomson, and Bloom syndrome, respectively (4, 5). The cells from BS patients display genomic instability; the hallmark of BS is an increase in the frequency of sister chromatid and interhomolog exchanges (1, 6). Because homologous recombination (HR) is responsible for chromosomal exchanges, it is thought that BLM helicase functions in regulating HR (7-9). Also, BLM helicase is required for faithful chromosome segregation (10) and repair of stalled replication forks (11, 12), the processes that are linked to HR (13-15). BLM was found to interact physically with RAD51, a key protein of HR (16) that catalyzes the central steps in HR including the search for homology and the exchange of strands between homologous ssDNA and dsDNA sequences (17). In cells, BLM forms nuclear foci, a subset of which co-localize with RAD51. Interestingly, the extent of RAD51 and BLM co-localization increases in response to ionizing radiation, indicating a possible role of BLM in the repair of DNA double-strand breaks (16).Biochemical studies suggest that BLM may perform several different functions in HR. BLM was shown to promote the dissociation of HR intermediates (D-loops) (18 -20), branch migration of Holliday junctions (21), and dissolution of double Holliday junctions acting in a complex with . BLM may also facilitate DNA synthesis during the repair process by unwinding the DNA template in front of the replication fork (25). In addition, BLM and its yea...

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The Hop2 and Mnd1 proteins act in concert with Rad51 and Dmc1 in meiotic recombination

Cited by 162 publications

References 33 publications

Identification of the meiotic life cycle stage of Trypanosoma brucei in the tsetse fly

Identification of the meiotic life cycle stage of Trypanosoma brucei in the tsetse fly

A Variant of the Breast Cancer Type 2 Susceptibility Protein (BRC) Repeat Is Essential for the RECQL5 Helicase to Interact with RAD51 Recombinase for Genome Stabilization

Bloom Syndrome Helicase Stimulates RAD51 DNA Strand Exchange Activity through a Novel Mechanism

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