Functional analysis of chromatin-associated proteins in Sordaria macrospora reveals similar roles for RTT109 and ASF1 in development and DNA damage response.

We performed a functional analysis of two potential partners of ASF1, a highly conserved histone chaperone that plays a crucial role in the sexual development and DNA damage resistance in the ascomycete Sordaria macrospora. ASF1 is known to be involved in nucleosome assembly and disassembly, binding histones H3 and H4 during transcription, replication and DNA repair and has direct and indirect roles in histone recycling and modification as well as DNA methylation, acting as a chromatin modifier hub for a large network of chromatin-associated proteins. Here, we functionally characterized two of these proteins, RTT109 and CHK2. RTT109 is a fungal-specific histone acetyltransferase, while CHK2 is an ortholog to PRD-4, a checkpoint kinase of Neurospora crassa that performs similar cell cycle checkpoint functions as yeast RAD53. Through the generation and characterization of deletion mutants, we discovered striking similarities between RTT109 and ASF1 in terms of their contributions to sexual development, histone acetylation, and protection against DNA damage. Phenotypic observations revealed a developmental arrest at the same stage in Δrtt109 and Δasf1 strains, accompanied by a loss of H3K56 acetylation, as detected by western blot analysis. Deletion mutants of rtt109 and asf1 are sensitive to the DNA damaging agent methyl methanesulfonate, but not hydroxyurea. In contrast, chk2 mutants are fertile and resistant to methyl methanesulfonate, but not hydroxyurea. Our findings suggest a close functional association between ASF1 and RTT109 in the context of development, histone modification, and DNA damage response, while indicating a role for CHK2 in separate pathways of the DNA damage response.

Using personal digital assistants to access drug information.

The use of personal digital assistants (PDAs) to access drug information in a health system is described. Given the widespread use of PDAs at an 872-bed university health system, an opportunity existed to provide current drug information to physicians via these devices. As part of the health system's intranet, extensive online content had been made available through a browser; extension to PDAs was a natural next step. There were two primary requirements: the ability to synchronize information with the database server when a PDA was used and the development of content and applications by using existing staff. Mobile enterprise software was chosen that supports multiple PDA platforms, is easy to use, and does not require programming skills. The software works through customized "channels," or collections of information from a content provider. The customized channel service works over the Internet. Two channels of content were created, an ambulatory care channel and an inpatient care channel. The ambulatory care channel contains a list of preferred ambulatory care agents, poison control information, the locations of outpatient pharmacies, drug information, and safety tips for prescribing. The inpatient channel contains the inpatient formulary, current news and events, information on currrent drug shortages and recalls, pharmacy contact information, and medication safety tips. When a user synchronizes his or her PDA, the software contacts the department's intranet servers and processes the request. The data are compressed and downloaded to the user's PDA. A university health system successfully used PDAs to access drug and other information.