Browsing by Subject "Dimers"

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    Oligomerization of human ATP-binding cassette transporters and its potential significance in human disease
    (Taylor & Francis, 2009) Mo, Wei; Zhang, Jian-Ting; Pharmacology and Toxicology, School of Medicine
    Human ATP-binding cassette transporters (ABC transporter) belong to an extremely important superfamily of membrane transporters. They use energy from ATP hydrolysis to transport a wide variety of substrates across the cellular membrane. Due to the physiological and pharmacological importance of their diverse substrates, ABC transporters have been shown to have close relationship with various human diseases such as cystic fibrosis and multi-drug resistance in cancer chemotherapy. While it has been thought traditionally that functional ABC transporters exist as monomeric full or dimeric half transporters, emerging evidence indicates that some ABC transporters oligomerize on cellular membranes and this oligomerization seems to have functional relevance. Therefore, this oligomerization process might be a promising drug target for ABC transporter-related human diseases, especially in overcoming multi-drug resistance in cancer chemotherapy. In this review, we perform a critical analysis of the past studies on the oligomerization of ABC transporters.
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    RAD50 Is Required for Efficient Initiation of Resection and Recombinational Repair at Random, y-Induced Double-Strand Break Ends
    (PLOS, 2009-09-18) Westmoreland, Jim; Ma, Wenjian; Yan, Yan; Van Hulle, Kelly; Malkova, Anna; Resnick, Michael A.; Biology, School of Science
    Resection of DNA double-strand break (DSB) ends is generally considered a critical determinant in pathways of DSB repair and genome stability. Unlike for enzymatically induced site-specific DSBs, little is known about processing of random “dirty-ended” DSBs created by DNA damaging agents such as ionizing radiation. Here we present a novel system for monitoring early events in the repair of random DSBs, based on our finding that single-strand tails generated by resection at the ends of large molecules in budding yeast decreases mobility during pulsed field gel electrophoresis (PFGE). We utilized this “PFGE-shift” to follow the fate of both ends of linear molecules generated by a single random DSB in circular chromosomes. Within 10 min after γ-irradiation of G2/M arrested WT cells, there is a near-synchronous PFGE-shift of the linearized circular molecules, corresponding to resection of a few hundred bases. Resection at the radiation-induced DSBs continues so that by the time of significant repair of DSBs at 1 hr there is about 1–2 kb resection per DSB end. The PFGE-shift is comparable in WT and recombination-defective rad52 and rad51 strains but somewhat delayed in exo1 mutants. However, in rad50 and mre11 null mutants the initiation and generation of resected ends at radiation-induced DSB ends is greatly reduced in G2/M. Thus, the Rad50/Mre11/Xrs2 complex is responsible for rapid processing of most damaged ends into substrates that subsequently undergo recombinational repair. A similar requirement was found for RAD50 in asynchronously growing cells. Among the few molecules exhibiting shift in the rad50 mutant, the residual resection is consistent with resection at only one of the DSB ends. Surprisingly, within 1 hr after irradiation, double-length linear molecules are detected in the WT and rad50, but not in rad52, strains that are likely due to crossovers that are largely resection- and RAD50-independent.