Targeting the Homologous Recombination Pathway in Cancer With a Novel Class of RAD51 Inhibitors.

Targeting DNA damage response (DDR) pathway has been proposed as an approach for amplifying tumor-specific replicative lesions. RAD51 plays a central role in the DDR process, and thus represents a promising anti-tumor target. We here report the discovery of a series of next generation RAD51 inhibitors that can prevent RAD51 foci formation.

Aquaporin-3 regulates endosome-to-cytosol transfer via lipid peroxidation for cross presentation.

Antigen cross presentation, whereby exogenous antigens are presented by MHC class I molecules to CD8+ T cells, is essential for generating adaptive immunity to pathogens and tumor cells. Following endocytosis, it is widely understood that protein antigens must be transferred from endosomes to the cytosol where they are subject to ubiquitination and proteasome degradation prior to being translocated into the endoplasmic reticulum (ER), or possibly endosomes, via the TAP1/TAP2 complex. Revealing how antigens egress from endocytic organelles (endosome-to-cytosol transfer, ECT), however, has proved vexing.

Protein Phosphatase 1 Down Regulates ZYG-1 Levels to Limit Centriole Duplication.

In humans perturbations of centriole number are associated with tumorigenesis and microcephaly, therefore appropriate regulation of centriole duplication is critical. The C. elegans homolog of Plk4, ZYG-1, is required for centriole duplication, but our understanding of how ZYG-1 levels are regulated remains incomplete.

Centrosomes are autocatalytic droplets of pericentriolar material organized by centrioles.

Centrosomes are highly dynamic, spherical organelles without a membrane. Their physical nature and their assembly are not understood. Using the concept of phase separation, we propose a theoretical description of centrosomes as liquid droplets.

The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites.

The mechanistic underpinnings of metastatic dormancy and reactivation are poorly understood. A gain-of-function cDNA screen reveals that Coco, a secreted antagonist of TGF-β ligands, induces dormant breast cancer cells to undergo reactivation in the lung. Mechanistic studies indicate that Coco exerts this effect by blocking lung-derived BMP ligands.

Limiting amounts of centrosome material set centrosome size in C. elegans embryos.

Background: The ways in which cells set the size of intracellular structures is an important but largely unsolved problem [1]. Early embryonic divisions pose special problems in this regard. Many checkpoints common in somatic cells are missing from these divisions, which are characterized by rapid reductions in cell size and short cell cycles [2].

Automated tracking and analysis of centrosomes in early Caenorhabditis elegans embryos.

Motivation: The centrosome is a dynamic structure in animal cells that serves as a microtubule organizing center during mitosis and also regulates cell-cycle progression and sets polarity cues. Automated and reliable tracking of centrosomes is essential for genetic screens that study the process of centrosome assembly and maturation in the nematode Caenorhabditis elegans.

Results: We have developed a fully automatic system for tracking and measuring fluorescently labeled centrosomes in 3D time-lapse images of early C.

Caveolin-1 tyrosine phosphorylation enhances paclitaxel-mediated cytotoxicity.

Caveolin-1 (CAV1), a highly conserved membrane-associated protein, is a putative regulator of cellular transformation. CAV1 is localized in the plasmalemma, secretory vesicles, Golgi, mitochondria, and endoplasmic reticulum membrane and associates with the microtubule cytoskeleton. Taxanes such as paclitaxel (Taxol) are potent anti-tumor agents that repress the dynamic instability of microtubules and arrest cells in the G(2)/M phase.

Distribution of labelled anti-tenascin antibodies and fragments after injection into intact or partly resected C6-gliomas in rats.

Introduction: For treatment of malignant glioma, radioimmunotherapy has become a valuable alternative for more than 2 decades. Surprisingly, very little is known about the distribution of intralesionally administered labelled antibodies or fragments. We investigated the migration of labelled antibodies and antibody fragments injected into intact and partly resected C6-glioma in rats at different times after injection.