Role of Blm and collaborating factors in recombination and survival following replication stress in Ustilago maydis

Inactivation of the structural gene for the RecQ family member, BLM in human, Sgs1 in budding yeast, or Rqh1 in fission yeast leads to inappropriate recombination, chromosome abnormalities, and disturbed replication fork progression. Studies with yeasts have demonstrated that auxiliary gene functions can contribute in overlapping ways with Sgs1 or Rqh1 to circumvent or overcome lesions in DNA caused by certain genotoxic agents. In the combined absence of these functions, recombination-mediated processes lead to severe loss of fitness. Here we performed a genetic study to determine the role of the Ustilago maydis Blm homolog in DNA repair and in alleviating replication stress. We characterized the single mutant as well as double mutants additionally deleted of genes encoding Srs2, Fbh1, Mus81, or Exo1. Unlike yeasts, neither the blm srs2, blm exo1. nor blm mus81 double mutant exhibited extreme loss of fitness. Inactivation of Brh2, the BRCA2 homolog, suppressed toxicity to hydroxyurea caused by loss of Blm function. However, differential suppression by Brh2 derivatives lacking the canonical DNA-binding region suggests that the particular domain structure comprising this DNA-binding region may be instrumental in promoting the observed hydroxyurea toxicity.This is the peer reviewed version of the paper: Mao, N., Kojić, M., & Holloman, W. K. (2009). Role of Blm and collaborating factors in recombination and survival following replication stress in Ustilago maydis. DNA Repair, 8(6), 752–759. [https://doi.org/10.1016/j.dnarep.2009.02.006]Published version: [https://imagine.imgge.bg.ac.rs/handle/123456789/343

Failure mechanism on sulfate attack and dissolved corrosion of diseased tunnel lining structure

To study the corrosion failure mechanism of tunnel lining structure subjected to sulfate attack and dissolved corrosion, site investigation was carried out on a diseased tunnel in Chongqing. The corrosion products were analyzed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. The results showed that the tunnel lining structure had been exposed to groundwater containing substantial concentrations of salts (SO42-, HCO3-, et al.) for many years, resulted that the concrete strength was lower than its design value. The formation of thaumasite made concrete lose its strength completely. Concrete structure would be destroyed when crystallization pressure exceeded the tensile strength of concrete. The tunnel also appeared dissolved corrosion which made the cement stone density and concrete strength reduce

The Telomere Capping Complex CST Has an Unusual Stoichiometry, Makes Multipartite Interaction with G-Tails, and Unfolds Higher-Order G-Tail Structures

The telomere-ending binding protein complex CST (Cdc13-Stn1-Ten1) mediates critical functions in both telomere protection and replication. We devised a co-expression and affinity purification strategy for isolating large quantities of the complete Candida glabrata CST complex. The complex was found to exhibit a 2∶4∶2 or 2∶6∶2 stoichiometry as judged by the ratio of the subunits and the native size of the complex. Stn1, but not Ten1 alone, can directly and stably interact with Cdc13. In gel mobility shift assays, both Cdc13 and CST manifested high-affinity and sequence-specific binding to the cognate telomeric repeats. Single molecule FRET-based analysis indicates that Cdc13 and CST can bind and unfold higher order G-tail structures. The protein and the complex can also interact with non-telomeric DNA in the absence of high-affinity target sites. Comparison of the DNA–protein complexes formed by Cdc13 and CST suggests that the latter can occupy a longer DNA target site and that Stn1 and Ten1 may contact DNA directly in the full CST–DNA assembly. Both Stn1 and Ten1 can be cross-linked to photo-reactive telomeric DNA. Mutating residues on the putative DNA–binding surface of Candida albicans Stn1 OB fold domain caused a reduction in its crosslinking efficiency in vitro and engendered long and heterogeneous telomeres in vivo, indicating that the DNA–binding activity of Stn1 is required for telomere protection. Our data provide insights on the assembly and mechanisms of CST, and our robust reconstitution system will facilitate future biochemical analysis of this important complex

Administration in Role-Based Access Control

Administration of large-scale RBAC systems is a challenging open problem. We propose a principled approach in designing and analyzing administrative models for RBAC. We identify six design requirements for administrative models of RBAC. These design requirements are motivated by three principles for designing security mechanisms: (1) flexibility and scalability, (2) psychological acceptability, and (3) economy of mechanism. We then use these requirements to analyze several approaches to RBAC administration, including ARBAC97 [21, 23, 22], SARBAC [4, 5], and the RBAC system in the Oracle DBMS. Based on these requirements and the lessons learned in analyzing existing approaches, we design UARBAC, a new family of administrative models for RBAC that has significant advantages over existing models

Usable Mandatory Integrity Protection for Operating Systems

Existing mandatory access control systems for operating systems are difficult to use. We identify several principles for designing usable access control systems and introduce the Usable Mandatory Integrity Protection (UMIP) model that adds usable mandatory access control to operating systems. The UMIP model is designed to preserve system integrity in the face of network-based attacks. The usability goals for UMIP are twofold. First, configuring a UMIP system should not be more difficult than installing and configuring an operating system. Second, existing applications and common usage practices can still be used under UMIP. UMIP has several novel features to achieve these goals. For example, it introduces several concepts for expressing partial trust in programs. Furthermore, it leverages information in the existing discretionary access control mechanism to derive file labels for mandatory integrity protection. We also discuss our implementation of the UMIP model for Linux using the Linux Security Modules framework, and show that it is simple to configure, has low overhead, and effectively defends against a number of network-based attacks.

Towards Analyzing Complex Operating System Access Control Configurations

An operating system relies heavily on its access control mechanisms to defend against local and remote attacks. The complexities of modern access control mechanisms and the scale of possible configurations are often overwhelming to system administrators and software developers. Therefore mis-configurations are very common and the security consequences are serious. Given the popularity and uniqueness of Microsoft Windows systems, it is critical to have a tool to comprehensively examine the access control configurations. However, current studies on Windows access control mechanisms are mostly based on known attack patterns. We propose a tool, WACCA, to systematically analyze the Windows configurations. Given the attacker’s initial abilities and goals, WACCA generates an attack graph based on interaction rules. The tool then automatically generates attack patterns from the attack graph. Each attack pattern represents attacks of the same nature. The attack subgraphs and instances are also generated for each pattern. Compared to existing solutions, WACCA is more comprehensive and does not rely on manually defined attack patterns. It also has a unique feature in that it models software vulnerabilities and therefore can find attacks that rely on exploiting these vulnerabilities. We study two attack cases on a Windows Vista host and discuss the analysis results

Dss1 Regulates Interaction of Brh2 with DNA

Brh2, the BRCA2 homologue in Ustilago maydis, plays a crucial role in homologous recombination by controlling Rad51. In turn, Brh2 is governed by Dss1, an intrinsically disordered protein that forms a tight complex with the C-terminal region of Brh2. This region of the protein associating with Dss1 is highly conserved in sequence and by comparison with mammalian BRCA2 corresponds to a part of the DNA binding domain with characteristic OB folds. The N-terminal region of Brh2 harbors a less-defined but powerful DNA binding site, the activity of which is revealed upon deletion of the C-terminal region. Full-length Brh2 complexed with Dss1 binds DNA slowly, while the N-terminal fragment binds quickly. The DNA binding activity of full-length Brh2 appears to correlate with dissociation of Dss1. Addition of Dss1 to the heterotypic Brh2-Dss1 complex attenuates DNA binding activity, but not by direct competition for the N-terminal DNA binding site. Conversely, the Brh2-Dss1 complex dissociates more quickly when DNA is present. These findings suggest a model in which binding of Brh2 to DNA is subject to allosteric regulation by Dss1