Mus81, a protein with homology to the XPF subunit of the ERCC1-XPF endonuclease, is important for replicational stress tolerance in both budding and fission yeast. Human Mus81 has associated endonuclease activity against structure-specific oligonucleotide substrates, including synthetic Holliday junctions. Mus81-associated endonuclease resolves Holliday junctions into linear duplexes by cutting across the junction exclusively on strands of like polarity. In addition, Mus81 protein abundance increases in cells following exposure to agents that block DNA replication. Taken together, these findings suggest a role for Mus81 in resolving Holliday junctions that arise when DNA replication is blocked by damage or by nucleotide depletion. Mus81 is not related by sequence to previously characterized Holliday junction resolving enzymes, and it has distinct enzymatic properties that suggest it uses a novel enzymatic strategy to cleave Holliday junctions.

Forty-seven bronchoalveolar lavage fluid samples from 16 human immunodeficiency virus (HIV)-infectedpatients were used to test the latency model of Pneumocystis infection in the human host. Identification of DNA sequence polymorphisms at 4 independent loci were used to genotype Pneumocystis jiroveci from the 35 samples that contained detectable P. jiroveci DNA. Eighteen of those 35 samples came from patients who did not have Pneumocystis pneumonia (PCP) and had confirmed alternative diagnoses. Seven patients had asymptomatic carriage of P. jiroveci over periods of р9.5 months after an episode of PCP, and in all 7 cases, a change in genotype from that in the original episode of PCP was observed. The absence of P. jiroveci DNA in one-fourth of the 47 samples and the observed changes in genotype during asymptomatic carriage do not support the latency model of infection. Asymptomatic carriage in HIV-infected patients may play a role in transmission of P. jiroveci and may even supply a reservoir for future infections.The route of transmission of human Pneumocystis infection is still not understood. It was long thought that Pneumocystis jiroveci organisms were acquired during childhood and persisted throughout life in the lungs in a dormant phase [1,2]. Subsequent immunosuppression of the host, resulting from a variety of causes, permitted the fungus to propagate and to cause disease. According to this theory of transmission, there was little reason to protect immunosuppressed adults from possible exposure to Pneumocystis; acquisition of the infection was thought to take place early in life and not at the time of immunosuppression. The latency hypothesis, however, has recently been challenged. Several studies have suggested that, in the immunocompetent human host, Pneumocystis organisms are frequently acquired and cleared by the immune system, rather than being acquired during childhood and persisting for a lifetime. This reinfection hypothesis has important public health implications, because it suggests that susceptible individuals could be protected from Pneumocystis infection.Data refuting the latency hypothesis come from animal studies. It has been shown in a rat model that Pneumocystis organisms were eliminated from the lungs after Pneumocystis pneumonia (PCP) and that persistence of latent organisms was limited [3]. Similar results have been obtained using the severe combined immunodeficiency (SCID) mouse model [4]. In addition, some studies of human infection have indicated the

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