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- Elvers, Ingegerd, et al.
(författare)
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CHK1 activity is required for continuous replication fork elongation but not stabilization of post-replicative gaps after UV irradiation
- 2012
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 40:17, s. 8440-8448
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Tidskriftsartikel (refereegranskat)abstract
- Ultraviolet (UV)-induced DNA damage causes an efficient block of elongating replication forks. The checkpoint kinase, CHK1 has been shown to stabilize replication forks following hydroxyurea treatment. Therefore, we wanted to test if the increased UV sensitivity caused by the unspecific kinase inhibitor caffeine-inhibiting ATM and ATR amongst other kinases-is explained by inability to activate the CHK1 kinase to stabilize replicative structures. For this, we used cells deficient in polymerase eta (Pol eta), a translesion synthesis polymerase capable of properly bypassing the UV-induced cis-syn TT pyrimidine dimer, which blocks replication. These cells accumulate gaps behind progressing replication forks after UV exposure. We demonstrate that both caffeine and CHK1 inhibition, equally retards continuous replication fork elongation after UV treatment. Interestingly, we found more pronounced UV-sensitization by caffeine than with the CHK1 inhibitor in clonogenic survival experiments. Furthermore, we demonstrate an increased collapse of replicative structures after caffeine treatment, but not after CHK1 inhibition, in UV-irradiated cells. This demonstrates that CHK1 activity is not required for stabilization of gaps induced during replication of UV-damaged DNA. These data suggest that elongation and stabilization of replicative structures at UV-induced DNA damage are distinct mechanisms, and that CHK1 is only involved in replication elongation.
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- Jensen, Klaus M. -E., et al.
(författare)
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Reconstructive urology in the Nordic countries - A hospital questionnaire survey
- 2001
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 35:3, s. 186-189
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Tidskriftsartikel (refereegranskat)abstract
- A hospital survey of adult reconstructive urologic surgery in the Nordic countries is presented. The response rate was 80% and included most general hospitals and university clinics. Despite similarities between the healthcare systems of the various countries several differences were found. Cystectomy was performed in a large number of institutions in all countries except Denmark. The annual number of orthotopic bladder substitutions per institution was calculated as three to four (range of medians for each country) and the number of continent cutaneous diversions as two to seven. Open urethral procedures were performed more frequently in Sweden than in the other countries. Surgery for penile curvature and implantation of three-component prostheses for erectile dysfunction was more commonly performed in Denmark and Iceland compared to Sweden.
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- Lundin, Cecilia, et al.
(författare)
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Different Roles for Nonhomologous End Joining and Homologous Recombination following Replication Arrest in Mammalian Cells
- 2002
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Ingår i: Molecular and Cellular Biology. - : American Society of Microbiology. - 0270-7306. ; 22:16, s. 5869-78
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Tidskriftsartikel (refereegranskat)abstract
- Homologous recombination (HR) and nonhomologous end joining (NHEJ) play overlapping roles in repair of DNA double-strand breaks (DSBs) generated during the S phase of the cell cycle. Here, we characterized the involvement of HR and NHEJ in the rescue of DNA replication forks arrested or slowed by treatment of hamster cells with hydroxyurea or thymidine. We show that the arrest of replication with hydroxyurea generates DNA fragmentation as a consequence of the formation of DSBs at newly replicated DNA. Both HR and NHEJ protected cells from the lethal effects of hydroxyurea, and this agent also increased the frequency of recombination mediated by both homologous and nonhomologous exchanges. Thymidine induced a less stringent arrest of replication and did not generate detectable DSBs. HR alone rescued cells from the lethal effects of thymidine. Furthermore, thymidine increased the frequency of DNA exchange mediated solely by HR in the absence of detectable DSBs. Our data suggest that both NHEJ and HR are involved in repair of arrested replication forks that include a DSB, while HR alone is required for the repair of slowed replication forks in the absence of detectable DSBs.
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- Mandenius, Carl-Fredrik, et al.
(författare)
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Quality-by-design for biotechnology-related pharmaceuticals.
- 2009
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Ingår i: Biotechnology journal. - : Wiley. - 1860-7314 .- 1860-6768. ; 4:5, s. 600-9
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Tidskriftsartikel (refereegranskat)abstract
- The following article is a report from a workshop on Quality-by-Design (QbD) held at the 7th European Symposium on Biochemical Engineering Science (7 September 2008, Faro, Portugal).The aim of the workshop was to provide an update on the present status of using QbD in biotechnology-related applications in the pharmaceutical industry. The report summarizes the essential parts of the presentations and covers the industrial, academic, and regulatory aspects of QbD. It concludes with recommendations for further work and development.
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