The role of hRev7, the accessory subunit of hPolζ, in translesion synthesis past DNA damage induced by benzo[a]pyrene diol epoxide (BPDE)

<p>Abstract</p> <p>Background</p> <p>DNA polymerase zeta (Polζ) is a specialized DNA polymerase that, unlike classical replicative polymerases, is capable of replicating past DNA lesions, i.e. of performing translesion synthesis (TLS). The catalytic subunit of hPolζ, hRev3, has been shown to play a critical role in DNA damage-induced mutagenesis in human cells, but less is known about the role of hRev7, the accessory subunit of hPolζ, in such mutagenesis. To address this question, we recently generated human fibroblasts with very significantly reduced levels of hRev7 protein and demonstrated that hRev7 is required to protect cells from ultraviolet_{(254 nm)}(UV) radiation-induced cytotoxicity and mutagenesis (McNally et al., DNA Repair 7 (2008) 597-604). The goal of the present study was to determine whether hRev7 is similarly involved in the tolerance of DNA damage induced by benzo[a]pyrene diol epoxide (BPDE), the reactive form of the widespread environmental carcinogen benzo[a]pyrene.</p> <p>Methods</p> <p>To determine whether hRev7 also plays a role in protecting human cells from the cytotoxicity and mutagenesis induced by benzo[a]pyrene diol epoxide (BPDE), cell strains with reduced hRev7 were compared to their parental strain and a vector control strain for the effect of BPDE on cell survival, induction of mutations, and the ability to progress through the cell cycle.</p> <p>Results</p> <p>The results show that cell strains with reduced hRev7 are more sensitive to the cytotoxic effect of BPDE than the control strains, and progress through S-phase at a slower rate than the control cells following BPDE treatment, indicating that hRev7, and likely hPolζ, is required for efficient bypass of BPDE-induced DNA lesions. However, neither the frequency nor kinds of mutations induced by BPDE in cells with reduced hRev7 differ significantly from those induced in the control strains, suggesting that hPolζ is not essential for inserting nucleotides opposite BPDE-induced DNA damage.</p> <p>Conclusions</p> <p>Taken together, our results which show that hRev7 is required for TLS past BPDE-induced DNA lesions but that it is not essential for inserting nucleotides opposite such lesions suggest a role for hPolζ in the extension step of translesion synthesis.</p

Genetic Analysis Workshop 14: microsatellite and single-nucleotide polymorphism marker loci for genome-wide scans.

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Residential care staff working knowledge of reporting restrictive practices within Intellectual Disability and Older Persons care settings: A scoping review

Introduction: This Restrictive practice is an intentional restriction of an individual’s voluntary movement or behaviour. Given the impingement of human rights associated with restrictive practice, many jurisdictions all over the world have advocated for a reduction in their use, highlighting the importance of reporting restrictive practice. However, a paucity of literature exists examining the knowledge of residential care staff regarding reporting restrictive practice. Aim: To examine the knowledge of residential care staff regarding the reporting of restrictive practices in intellectual disability and older persons care settings. Methods: A scoping review referenced to JBI and PRISMA guidelines was used. The studies were retrieved from a library multi-search function of various databases. Sixteen studies were included in the final analysis. Findings: Findings demonstrate that residential staff lack knowledge of what defines a restrictive practice and find the reporting system as unnecessary, time consuming and burdensome. The identified barriers to reporting restrictive practice included: fear, lack of clear guidelines and awareness of the reporting system, lack of time, and staff shortages. While the facilitators included awareness campaigns, availability of appropriate reporting structures, and managerial support. Conclusion: This review suggests that improvements in terms of residential staff understanding of and reporting of restrictive practice is required. Moreover, this review has the potential to assist policymakers to understand the individual, organisational and regulatory barriers and facilitators to reporting restrictive practice within intellectual disability and older persons care settings