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Schizosaccharomyces pombe Crb2 is a checkpoint mediator required for the cellular response to DNA damage. Like human 53BP1 and Saccharomyces cerevisiae Rad9 it contains Tudor 2 and BRCT 2 domains. Crb2-Tudor 2 domain interacts with methylated H4K20 and is required for recruitment to DNA dsDNA breaks. The BRCT 2 domain is required for dimerization, but its precise role in DNA damage repair and checkpoint signaling is unclear. The crystal structure of the Crb2-BRCT 2 domain, alone and in complex with a phosphorylated H2A.1 peptide, reveals the structural basis for dimerization and direct interaction with ␥-H2A. The outermost "effector" layer is provided by the checkpoint kinases, Chk1 and Chk2/Cds1/Rad53 (Bartek and Lukas 2003), which phosphorylate a broad range of substrates, including Cdc25 phosphatases (Bartek and Lukas 2001;Ahn et al. 2003), Pds1/securin (Wang et al. 2001), p53 (Hirao et al. 2000, BRCA1 (Lee et al. 2000), and E2F1 (Stevens et al. 2003), and thereby communicate with the cellular mechanisms regulating cell cycle and (in multicellular eukaryotes) apoptosis.Connecting and communicating between the DNA damage sensors and effectors are a group of adaptor or mediator proteins that commonly contain tandem repeats of the BRCT domain, first identified in S. pombe

A surface acoustic wave-based sample delivery and ionization method that requires minimal to no sample pretreatment and that can operate under ambient conditions is described. This miniaturized technology enables real-time, rapid, and high-throughput analysis of trace compounds in complex mixtures, especially high ionic strength and viscous samples that can be challenging for conventional ionization techniques such as electrospray ionization. This technique takes advantage of high order surface acoustic wave (SAW) vibrations that both manipulate small volumes of liquid mixtures containing trace analyte compounds and seamlessly transfers analytes from the liquid sample into gas phase ions for mass spectrometry (MS) analysis. Drugs in human whole blood and plasma and heavy metals in tap water have been successfully detected at nanomolar concentrations by coupling a SAW atomization and ionization device with an inexpensive, paper-based sample delivery system and mass spectrometer. The miniaturized SAW ionization unit requires only a modest operating power of 3 to 4 W and, therefore, provides a viable and efficient ionization platform for the real-time analysis of a wide range of compounds.