As part of the DNA damage response (DDR) network, the tumour suppressor Breast cancer susceptibility gene 1 (BRCA1) is activated to facilitate DNA repair, transcription and cell cycle control. BRC-1, the Caenorhabditis elegans ortholog of BRCA1, has conserved function in DNA double strand break repair, wherein a loss of brc-1 results in high levels of germline apoptosis. BRAP2/IMP was initially identified as a BRCA1 associated binding protein and previously we have shown that the C. elegans brap-2 deletion mutant experiences BRC-1 dependent larval arrest when exposed to low concentrations of paraquat. Since BRC-1 function in the germline is conserved, we wanted to determine the role of BRAP-2 in DNA damage induced germline apoptosis in C. elegans. We examined levels of germ cell death following DNA damage and found that brap-2(ok1492) mutants display reduced levels of germline apoptosis when compared to the wild type, and the loss of brap-2 significantly reduced germ cell death in brc-1 mutant animals. We also found increased mRNA levels of skn-1 following DNA damage in brap-2 mutants and that skn-1 RNAi knockdown in brap-2;brc-1 double mutants and a loss of pmk-1 mutation in brap-2 mutants increased apoptosis to wild type levels, indicating that brap-2 promotion of cell survival requires PMK-1 and SKN-1. Since mammalian BRAP2 has been shown to bind the AKT phosphatase PHLPP1/2, it suggests that BRAP2 could be involved in the Insulin/Insulin-like growth factor Signaling (IIS) pathway. We found that this interaction is conserved between the C. elegans homologs and that a loss of akt-1 in brap-2 mutants increased germline apoptosis. Thus in response to DNA damage, our findings suggest that BRAP-2 is required to attenuate the pro-cell survival signals of AKT-1 and PMK-1/SKN-1 to promote DNA damage induced germline apoptosis.
Nanostructured polymers contain features smaller than 100 nm that are useful in a wide range of areas, including photonics, biomedical materials, and environmental applications. Out of the myriad of nanostructured polymers, surfactant-templated polymers are versatile because of their ability to have tunable domain sizes, structure, and composition. This work addresses the gap between the formulation with industrial-grade polymerizable surfactants and the final structure of the polymer, using the hydrophilic− lipophilic difference (HLD) and net-average curvature (NAC) frameworks. HLD indicates the proximity of the formulation (surfactant and oil monomer selection, temperature, electrolyte concentration) to the phase inversion point, where HLD = 0. NAC uses the HLD to determine the curvature of the surfactant−oil−water interface, leading not only to the size and shape of micelles and bicontinuous isotropic (L 3 ) systems but also to defining the most likely regions for lyotropic liquid crystal (LLC) existence and phase separation in ternary phase diagrams. Polymerizing LLC fluids produced nanostructured polymers with similar LLC structures that were highly swellable, but with low compressive strength. Polymerizing L 3 fluids produced strong, but less water-swellable nanostructured polymers with a similar characteristic length to the parent L 3 microemulsion. The relatively small scale of the parent LLC (∼6−8 nm) or L 3 (∼3−4 nm) systems is consistent with the translucent nature of the polymers produced and the HLD-NAC predicted sizes.
Background. Mutations in C. elegans can produce visible and quantifiable defects in morphology, lifespan, and development. BRAP2/IMP (BRCA1-associated binding protein 2) has been characterized as an E3 ubiquitin ligase, a general cytoplasmic retention factor, a potential scaffold protein, and is found to be widely expressed throughout various mammalian tissues, most highly in testes. However, its role in the development or health of these tissues has not been addressed. Results. The focus of this study is to determine the role of BRAP-2 in C. elegans germline development. We determined that brap-2 mutants display defects in germline morphology and a reduction in brood size. We also found that chromosomal abnormalities and embryonic lethality are elevated in brap-2 mutants following DNA damage, suggesting a potential role for BRAP-2 in facilitating DNA repair. Conclusions. Our findings indicate that BRAP-2 is required for C. elegans germline health and identifies a novel role for BRAP-2 in germline development.
Background. Mutations in C. elegans can produce visible and quantifiable defects in morphology, lifespan, and development. BRAP2/IMP (BRCA1-associated binding protein 2) has been characterized as an E3 ubiquitin ligase, a general cytoplasmic retention factor, a potential scaffold protein, and is found to be widely expressed throughout various mammalian tissues, most highly in testes. However, its role in the development or health of these tissues has not been addressed. Results. The focus of this study is to determine the role of BRAP-2 in C. elegans germline development. We determined that brap-2 mutants display defects in germline morphology and a reduction in brood size. We also found that chromosomal abnormalities and embryonic lethality are elevated in brap-2 mutants following DNA damage, suggesting a potential role for BRAP-2 in facilitating DNA repair. Conclusions. Our findings indicate that BRAP-2 is required for C. elegans germline health and identifies a novel role for BRAP-2 in germline development.
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