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Summary: The tumor suppressor BRCA2 is essential for homologous recombination (HR), replication fork stability, and DNA interstrand crosslink repair in vertebrates. We identify HSF2BP, a protein previously described as testis specific and not characterized functionally, as an interactor of BRCA2 in mouse embryonic stem cells, where the 2 proteins form a constitutive complex. HSF2BP is transcribed in all cultured human cancer cell lines tested and elevated in some tumor samples. Inactivation of the mouse Hsf2bp gene results in male infertility due to a severe HR defect during spermatogenesis. The BRCA2-HSF2BP interaction is highly evolutionarily conserved and maps to armadillo repeats in HSF2BP and a 68-amino acid region between the BRC repeats and the DNA binding domain of human BRCA2 (Gly2270-Thr2337) encoded by exons 12 and 13. This region of BRCA2 does not harbor known cancer-associated missense mutations and may be involved in the reproductive rather than the tumor-suppressing function of BRCA2. : BRCA2 is a key homologous recombination mediator in vertebrates. Brandsma et al. show that it directly interacts with a testis-expressed protein, HSF2BP, and that male mice deficient for HSF2BP are infertile due to a meiotic recombination defect. They also find that HSF2BP contributes to DNA repair in mouse embryonic stem cells. Keywords: HSF2BP, BRCA2, homologous recombination, meiosis, spermatogenesis

Numerous neurohumoral factors such as endothelin (ET)-1 and angiotensin (Ang) II as well as the stretchstimulus act concertedly in the in vivo overloaded heart in inducing hypertrophy and failure. The primary cultureof rat neonatal cardiomyocytes is the only in vitro model that allows the comparative analysis of growthresponses and signaling events in response to different stimuli. In the present study, we examined stretched ratcardiomyocytes grown on flexible bottomed culture plates for hypertrophic growth responses (protein synthesis,protein/DNA ratio, and cell volume), F-actin filaments rearrangement (by confocal laser scanningmicroscopy), and for signaling events (activation of phospholipase C [PLC]-β, protein kinase C [PKC], mitogenactivatedprotein [MAP] kinases) and compared these responses with ET-1 (10-8 M)-stimulated cells. Cyclicstretch for 48 h induced hypertrophic growth in cardiomyocytes indicated by increases in the rate of protein synthesis,cell volume, and diameter, which were less pronounced in comparison to stimulation by ET-1. Duringcyclic stretch, we observed disoriented F-actin, particularly stress-fibers whereas during ET-1 stimulation, Factinsrearranged clearly in alignment with sarcomeres and fibers. The upstream part of signaling by cyclicstretch did not follow the PLCβ-PKC cascade, which, in contrast, was strongly activated during ET-1 stimulation.Cyclic stretch and, to greater extent, ET-1 stimulated downstream signaling through ERK, p38 MAP kinase,and JNK pathways, but the involvement of tyrosine kinase and PI3 kinase-Akt signaling during cyclic stretchcould not be proven. Taken together, our results demonstrate that both cyclic stretch and ET-1 induce hypertrophicresponses in cardiomyocytes with different effects on organization of F-actin stress fibers in case ofstretch. Furthermore, on the short-term basis, cyclical stretch, unlike ET-1, mediates its hypertrophic responsenot through activation of PLC-β and PKC but more likely through integrin-linked pathways, which both lead todownstream activation of the MAP kinase family. [ABSTRACT FROM AUTHOR]