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We have synthesized triple helix forming oligonucleotides (TFOs) that target a psoralen (pso) interstrand crosslink to a specific chromosomal site in mammalian cells. Mutagenesis of the targeted crosslinks results in base substitutions and deletions. Identification of the gene products involved in mutation formation is important for developing practical applications of pso-TFOs, and may be informative about the metabolism of other interstrand crosslinks. We have studied mutagenesis of a pso-TFO genomic crosslink in repair proficient and deficient cells. Deficiencies in non homologous end joining and mismatch repair do not influence mutation patterns. In contrast, the frequency of base substitutions is dependent on the activity of ERCC1/XPF and polymerase zeta, but independent of other nucleotide excision repair (NER) or transcription coupled repair (TCR) genes. In NER/TCR deficient cells the frequency of deletions rises, indicating that in wild-type cells NER/TCR functions divert pso-TFO crosslinks from processes that result in deletions. We conclude that targeted pso-TFO crosslinks can enter genetically distinct mutational routes that resolve to base substitutions or deletions.

This article is available open access through the publisher’s website. Copyright @ 2013 The Authors. This article explores the readiness of gerontological social work in the UK for meeting the challenges of an ageing society by investigating the focus on work with older people in social work education and the scope of gerontological social work research. The discussion draws on findings from two exploratory studies: a survey of qualifying master's programmes in England and a survey of the content relating to older people over a six-year period in four leading UK social work journals. The evidence from master's programmes suggests widespread neglect of ageing in teaching content and practice learning. Social work journals present a more nuanced picture. Older people emerge within coverage of generic policy issues for adults, such as personalisation and safeguarding, and there is good evidence of the complexity of need in late life. However, there is little attention to effective social work interventions, with an increasingly diverse older population, or to the quality of gerontological social work education. The case is made for infusing content on older people throughout the social work curriculum, for extending practice learning opportunities in social work with older people and for increasing the volume and reporting of gerontological social work research. Brunel Institute for Ageing Studies