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| 2. |
- Elvers, Ingegerd, et al.
(författare)
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UV stalled replication forks restart by re-priming in human fibroblasts
- 2011
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 39:16, s. 7049-7057
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Tidskriftsartikel (refereegranskat)abstract
- Restarting stalled replication forks is vital to avoid fatal replication errors. Previously, it was demonstrated that hydroxyurea-stalled replication forks use an active restart mechanism or rescue replication by new origin firing. Using the DNA fiber assay, we find to our surprise no evidence that UV-damaged replication forks are arrested and only detect a slightly reduced fork speed on a UV-damaged template. Interestingly, no evidence for UV-induced fork stalling was observed even in translesion synthesis defective, Polηmut cells. In contrast, using an assay to measure DNA molecule elongation at the fork, we observe that DNA elongation is severely blocked, particularly in UV-damaged Polηmut cells. In conclusion, these data suggest that UV-blocked replication forks restart effectively through re-priming. If left unfilled, the gap behind a re-primed fork may collapse into a DNA double-strand break that is repaired by a recombination pathway, similar to the fate of replication forks collapsed after hydroxyurea treatment.
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| 3. |
- Groth, Camilla, et al.
(författare)
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T-shaped craft researchers' contribution in transdisciplinary research projects
- 2024
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Ingår i: JOURNAL OF MATERIAL CULTURE. - 1359-1835 .- 1460-3586. ; 29:2
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Tidskriftsartikel (refereegranskat)abstract
- Transdisciplinary project groups are promoted as a way for coping with the growing complexity of research environments. In the context of archaeology and conservation, the knowhow of practitioner-researchers in crafts has potential in supporting the reconstruction of past events as well as the material and technical background factors. As education in the arts and crafts have gradually moved from the workshops into academic institutions, artisans enter higher education and can pursue research careers. In cases where an artisan with longitudinal craft experience conducts research training in a related area, such as archaeology or conservation, we can speak of T-shaped practitioners. In this article, we will present three examples of research conducted by Scandinavian practitioner-researchers who are professional crafts practitioners in wood, but also archaeologists / conservators. We discuss the potentials of practitioner-researchers in craft for facilitating experiential knowledge transfer between project members of different disciplines.
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| 4. |
- Groth, Camilla, et al.
(författare)
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Why should archaeologists work with craftspersons?
- 2019
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Ingår i: 25th annual meeting of the European Association of Archaeologists; Beyond paradigms, Bern September 5-7, 2019.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Interdisciplinary research is promoted as a way forward in coping with the growing complexity of research environments. In the context of archaeology, the knowhow of crafts persons has a great potential in aiding in the reconstruction of past events as well as in the understanding of the many background factors that shaped those events. While crafts persons have traditionally been occupied with their own craft rather than pursuing academic careers, the situation is now changing as education in the arts and crafts have moved into the academic institutions. The growing number of crafts persons with an academic interest and skills make these practitioners ample T-shaped collaborators especially in the field of archaeology and conservation. In this presentation we will discuss three cases of collaborative practices between archaeologists/conservators and craftspeople and point to the new breed of practitioner-researchers who incorporate both of these practices in their academic profiles. Drawing on embodied cognition theory and auto-ethnographical reflections, we will dive deep into the crafts persons experiential and embodied knowing and point to the importance of the sensory spectrum in this context. Also, aspects of empathy and affect emerge in this process. Through this analysis we will present the possible benefits and challenges that interdisciplinary teams can expect when inviting crafts people into their research teams.
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| 5. |
- Groth, Petra, et al.
(författare)
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Methylated DNA Causes a Physical Block to Replication Forks Independently of Damage Signalling, O-6-Methylguanine or DNA Single-Strand Breaks and Results in DNA Damage
- 2010
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 402:1, s. 70-82
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Tidskriftsartikel (refereegranskat)abstract
- Even though DNA alkylating agents have been used for many decades in the treatment of cancer, it remains unclear what happens when replication forks encounter alkylated DNA. Here, we used the DNA fibre assay to study the impact of alkylating agents on replication fork progression. We found that the alkylator methyl methanesulfonate (MMS) inhibits replication elongation in a manner that is dose dependent and related to the overall alkylation grade. Replication forks seem to be completely blocked as no nucleotide incorporation can be detected following 1 h of MMS treatment. A high dose of 5 mM caffeine, inhibiting most DNA damage signalling, decreases replication rates overall but does not reverse MMS-induced replication inhibition, showing that the replication block is independent of DNA damage signalling. Furthermore, the block of replication fork progression does not correlate with the level of DNA single-strand breaks. Overexpression of O-6-methylguanine (O6meG)-DNA methyltransferase protein, responsible for removing the most toxic alkylation, O6meG, did not affect replication elongation following exposure to N-methyl-M-nitro-N-nitrosoguanidine. This demonstrates that O6meG lesions are efficiently bypassed in mammalian cells. In addition, we find that MMS-induced gamma H2AX foci co-localise with 53BP1 foci and newly replicated areas, suggesting that DNA double-strand breaks are formed at MMS-blocked replication forks. Altogether, our data suggest that N-alkylations formed during exposure to alkylating agents physically block replication fork elongation in mammalian cells, causing formation of replication-associated DNA lesions, likely double-strand breaks.
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| 6. |
- Rafat, Mehrdad, et al.
(författare)
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Composite core-and-skirt collagen hydrogels with differential degradation for corneal therapeutic applications
- 2016
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 83, s. 142-155
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Tidskriftsartikel (refereegranskat)abstract
- Scarcity of donor tissue to treat corneal blindness and the need to deliver stem cells or pharmacologic agents to ensure corneal graft survival are major challenges. Here, new composite collagen-based hydrogels are developed as implants to restore corneal transparency while serving as a possible reservoir for cells and drugs. The composite hydrogels have a centrally transparent core and embedded peripheral skirt of adjustable transparency and degradability, with the skirt exhibiting faster degradation in vitro. Both core and skirt supported human epithelial cell populations in vitro and the skirt merged homogeneously with the core material to smoothly distribute a mechanical load in vitro. After in vivo transplantation in rabbit corneas over three months, composites maintained overall corneal shape and integrity, while skirt degradation could be tracked in vivo and non-invasively due to partial opacity. Skirt degradation was associated with partial collagen breakdown, thinning, and migration of host stromal cells and macrophages, while the central core maintained integrity and transparency as host cells migrated and nerves regenerated.IMPACT:This study indicates the feasibility of a collagen-based composite hydrogel to maintain corneal stability and transparency while providing a degradable peripheral reservoir for cell or substance release.
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| 7. |
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| 8. |
- Vare, Daniel, et al.
(författare)
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DNA interstrand crosslinks induce a potent replication block followed by formation and repair of double strand breaks in intact mammalian cells
- 2012
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Ingår i: DNA Repair. - : Elsevier BV. - 1568-7864 .- 1568-7856. ; 11:12, s. 976-985
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Tidskriftsartikel (refereegranskat)abstract
- DNA interstrand crosslinks (ICLs) are highly toxic lesions that covalently link both strands of DNA and distort the DNA helix. Crosslinking agents have been shown to stall DNA replication and failure to repair ICL lesions before encountered by replication forks may induce severe DNA damage. Most knowledge of the ICL repair process has been revealed from studies in bacteria and cell extracts. However, for mammalian cells the process of ICL repair is still unclear and conflicting data exist. In this study we have explored the fate of psoralen-induced ICLs during replication, by employing intact mammalian cells and novel techniques. By comparative studies distinguishing between effects by monoadducts versus ICLs, we have been able to link the block of replication to the ICLs induction. We found that the replication fork was equally blocked by ICLs in wild-type cells as in cells deficient in ERCC1/XPF and XRCC3. The formation of ICL induced double strand breaks (DSBs), detected by formation of 53PB1 foci, was equally induced in the three cell lines suggesting that these proteins are involved at a later step of the repair process. Furthermore, we found that forks blocked by ICLs were neither bypassed, restarted nor restored for several hours. We propose that this process is different from that taking place following monoadduct induction by UV-light treatment where replication bypass is taking place as an early step. Altogether our findings suggest that restoration of an ICL blocked replication fork, likely initiated by a DSB occurs relatively rapidly at a stalled fork, is followed by restoration, which seems to be a rather slow process in intact mammalian cells.
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