Bloom's syndrome (BS) is a rare autosomal recessive disorder characterized by pre-and postnatal growth deficiency, immunodeficiency, and a tremendous predisposition to a wide variety of cancers. Cells from BS individuals are characterized by a high incidence of chromosomal gaps and breaks, elevated sister chromatid exchange, quadriradial formations, and locus-specific mutations. BS is the consequence of mutations that lead to loss of function of BLM, a gene encoding a helicase with homology to the RecQ helicase family. To delineate the role of BLM in DNA replication, recombination, and repair we used a yeast two-hybrid screen to identify potential protein partners of the BLM helicase. The C terminus of BLM interacts directly with MLH1 in the yeast-two hybrid assay; far Western analysis and co-immunoprecipitations confirmed the interaction. Cell extracts deficient in BLM were competent for DNA mismatch repair. These data suggest that the BLM helicase and MLH1 function together in replication, recombination, or DNA repair events independent of single base mismatch repair.Bloom's syndrome (BS) 1 is a rare autosomal recessive disorder characterized by immunodeficiency, short stature, male infertility, and an increased risk of a broad spectrum of cancers (1). Cells isolated from BS individuals are characterized by cytogenetic abnormalities, with the hallmark feature of hyperrecombination between sister chromatids. BS chromosomes also display increased levels of breaks, translocations, quadriradial formations, and telomeric associations (2).The gene mutated in BS was positionally cloned and named BLM; it encodes a 1417-amino acid protein with strong homology to the Escherichia coli RecQ family of DNA and RNA helicases (3). The E. coli RecQ helicase participates in homologous recombination and suppresses illegitimate recombination (4, 5). Other eukaryotic RecQ family members include Sgs1p from Saccharomyces cerevisiae and Rqh1p from Schizosaccharomyces pombe; loss of function of either of these helicases results in genomic instability (6, 7). Mutations in other human RecQ helicases result in the rare autosomal recessive disorders Werner's syndrome and Rothmund-Thomson syndrome, also characterized by chromosomal instability and cancer predisposition (8, 9).The BLM helicase unwinds duplex DNA from 3Ј to 5Ј in the presence of ATP (10, 11). It also selectively recognizes and promotes branch migration of Holliday junctions in vitro (12). BLM can be found in a large protein complex in the nucleus with other proteins involved in DNA repair such as BRCA1, ATM, MLH1, MSH2, MSH6, and replication factor C (13). However, direct interactions of BLM have only been demonstrated biochemically with replication protein A (RPA) and topoisomerase III␣ (14 -16). These experiments suggest that the BLM helicase interacts with a variety of nuclear proteins to perform functions in DNA replication, recombination, or repair.To understand the role of the BLM helicase in maintaining genomic stability, a yeast two-hybrid screen was used to identify...

In this study, interleukin-5 (IL-5) transgenic mice with lifelong eosinophilia were assessed for resistance to primary infections with two tissue-invading nematodes, Nippostrongylus brasiliensisand Toxocara canis. Relative to nontransgenic littermates, three lines of IL-5 transgenic mice with varying degrees of eosinophilia all displayed enhanced resistance to N. brasiliensis. Although the timing of final worm expulsion was similar in transgenic and nontransgenic hosts, intestinal worms in transgenic mice were fewer in number throughout infection, failed to increase in size over the course of the infection, and were much less fecund. In contrast, T. canis larvae were recovered in similar numbers from tissues of transgenic mice with “low” or “high” eosinophilia and from nontransgenic mice. These results and other data suggest that eosinophils can contribute to host resistance to some parasite species. Parasite transit time through the host may correlate with relative sensitivity to eosinophils.

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