| 1. |
- Duro, Eris, et al.
(författare)
-
Identification of the MMS22L-TONSL Complex that Promotes Homologous Recombination
- 2010
-
Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 40:4, s. 632-644
-
Tidskriftsartikel (refereegranskat)abstract
- Budding yeast Mms22 is required for homologous recombination (HR)-mediated repair of stalled or broken DNA replication forks. Here we identify a human Mms22-like protein (MMS22L) and an MMS22L-interacting protein, NF kappa BIL2/TONSL. Depletion of MMS22L or TONSL from human cells causes a high level of double-strand breaks (DSBs) during DNA replication. Both proteins accumulate at stressed replication forks, and depletion of MMS22L or TONSL from cells causes hypersensitivity to agents that cause S phase-associated DSBs, such as topoisomerase (TOP) inhibitors. In this light, MMS22L and TONSL are required for the HR-mediated repair of replication fork-associated DSBs. In cells depleted of either protein, DSBs induced by the TOP1 inhibitor camptothecin are resected normally, but the loading of the RAD51 recombinase is defective. Therefore, MMS22L and TONSL are required for the maintenance of genome stability when unscheduled DSBs occur in the vicinity of DNA replication forks.
|
|
| 2. |
- MacArtney, John I., et al.
(författare)
-
The convivial and the pastoral in patient–doctor relationships : a multi-country study of patient stories of care, choice and medical authority in cancer diagnostic processes
- 2020
-
Ingår i: Sociology of Health and Illness. - : Wiley. - 0141-9889 .- 1467-9566. ; 42:4, s. 844-861
-
Tidskriftsartikel (refereegranskat)abstract
- Experiences of cancer diagnosis are changing in light of both the increasingly technological-clinical diagnostic processes and the socio-political context in which interpersonal relations take place. This has raised questions about how we might understand patient–doctor relationship marked by asymmetries of knowledge and social capital, but that emphasise patients’ empowered choices and individualised care. As part of an interview study of 155 participants with bowel or lung cancer across Denmark, England and Sweden, we explored participants’ stories of the decisions made during their cancer diagnostic process. By focusing on the intersections of care, choice and medical authority – a convivial pastoral dynamic – we provide a conceptual analysis of the normative ambivalences in people's stories of their cancer diagnosis. We found that participants drew from care, choice and medical authority to emphasise their relationality and interdependence with their doctors in their stories of their diagnosis. Importantly negotiations of an asymmetrical patient–doctor relationship were part of an on-going realisation of the healthcare processes as a human endeavour. We were therefore able to draw attention to the limitations of dichotomising emancipatory-empowerment discourses and argue for a theorisation of the patient–doctor relationship as a contextually bounded and relationally ambivalent humanity.
|
|
| 3. |
- MacArtney, John, et al.
(författare)
-
Patients' initial steps to cancer diagnosis in Denmark, England and Sweden : what can a qualitative, cross-country comparison of narrative interviews tell us about potentially modifiable factors?
- 2017
-
Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 7:11
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To illuminate patterns observed in International Cancer Benchmarking Programme studies by extending understanding of the various influences on presentation and referral with cancer symptoms.DESIGN: Cross-country comparison of Denmark, England and Sweden with qualitative analysis of in-depth interview accounts of the prediagnostic process in lung or bowel cancer.PARTICIPANTS: 155 women and men, aged between 35 and 86 years old, diagnosed with lung or bowel cancer in 6 months before interview.SETTING: Participants recruited through primary and secondary care, social media and word of mouth. Interviews collected by social scientists or nurse researchers during 2015, mainly in participants' homes.RESULTS: Participants reported difficulties in interpreting diffuse bodily sensations and symptoms and deciding when to consult. There were examples of swift referrals by primary care professionals in all three countries. In all countries, participants described difficulty deciding if and when to consult, highlighting concerns about access to general practitioner appointments and overstretched primary care services, although this appears less prominent in the Swedish data. It was not unusual for there to be more than one consultation before referral and we noted two distinct patterns of repeated consultation: (1) situations where the participant left the primary care consultation with a plan of action about what should happen next; (2) participants were unclear about under which conditions to return to the doctors. This second pattern sometimes extended over many weeks during which patients described uncertainty, and sometimes frustration, about if and when they should return and whether there were any other feasible investigations. The latter pattern appeared more evident in the interviews in England and Denmark than Sweden.CONCLUSION: We suggest that if clear action plans, as part of safety netting, were routinely used in primary care consultations then uncertainty, false reassurance and the inefficiency and distress of multiple consultations could be reduced.
|
|
| 4. |
- MacKay, Craig, et al.
(författare)
-
Identification of KIAA1018/FAN1, a DNA Repair Nuclease Recruited to DNA Damage by Monoubiquitinated FANCD2
- 2010
-
Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 142:1, s. 65-76
-
Tidskriftsartikel (refereegranskat)abstract
- DNA interstrand crosslinks (ICLs) are highly toxic because they block the progression of replisomes. The Fanconi Anemia (FA) proteins, encoded by genes that are mutated in FA, are important for repair of ICLs. The FA core complex catalyzes the monoubiquitination of FANCD2, and this event is essential for several steps of ICL repair. However, how monoubiquitination of FANCD2 promotes ICL repair at the molecular level is unknown. Here, we describe a highly conserved protein, KIAA1018/MTMR15/FAN1, that interacts with, and is recruited to sites of DNA damage by, the monoubiquitinated form of FANCD2. FAN1 exhibits endonuclease activity toward 50 flaps and has 5' exonuclease activity, and these activities are mediated by an ancient VRR_nuc domain. Depletion of FAN1 from human cells causes hypersensitivity to ICLs, defects in ICL repair, and genome instability. These data at least partly explain how ubiquitination of FANCD2 promotes DNA repair.
|
|
| 5. |
- Malmström, Marlene, et al.
(författare)
-
It is important that the process goes quickly, isn't it?” A qualitative multi-country study of colorectal or lung cancer patients’ narratives of the timeliness of diagnosis and quality of care
- 2018
-
Ingår i: European Journal of Oncology Nursing. - : Elsevier BV. - 1462-3889 .- 1532-2122. ; 34, s. 82-88
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The emphasis on early diagnosis to improve cancer survival has been a key factor in the development of cancer pathways across Europe. The aim of this analysis was to explore how the emphasis on early diagnosis and timely treatment is reflected in patient's accounts of care, from the first suspicion of colorectal or lung cancer to their treatment in Denmark, England and Sweden. Method: We recruited 155 patients in Denmark, England and Sweden who were within six months of being diagnosed with lung or colorectal cancer. Data were collected via semi-structured narrative interviews and analysed using a thematic approach. Results: Participants’ accounts of quality of care were closely related to how quickly (or not) diagnosis, treatment and/or healthcare processes went. Kinetic metaphors as a description of care (such as treadmill) could be interpreted positively as participants were willing to forgo some degree of control and accept disruption to their lives to ensure more timely care. Drawing on wider cultural expectations of the benefits of diagnosing and treating cancer quickly, some participants were concerned that the waiting times between interventions might allow time for the cancer to grow. Conclusions: Initiatives emphasising the timeliness of diagnosis and treatment are reflected in the ways some patients experience their care. However, these accounts were open to further contextualisation about what speed of healthcare processes meant for evaluating the quality of their care. Healthcare professionals could therefore be an important patient resource in providing reassurance and support about the timeliness of diagnosis or treatment.
|
|
| 6. |
- Ziebland, Sue, et al.
(författare)
-
How wide is the Goldilocks Zone in your health system?
- 2019
-
Ingår i: Journal of Health Services Research and Policy. - : Sage Publications. - 1355-8196 .- 1758-1060. ; 24:1, s. 52-56
-
Tidskriftsartikel (refereegranskat)abstract
- In astrophysics, the 'Goldilocks Zone' describes the circumstellar habitable zone, in which planets, sufficiently similar to Earth, could support human life. The children's story of Goldilocks and the Three Bears, one of the most popular fairy tales in the English language, uses this metaphor to describe conditions for life that are neither too hot nor too cold and neither too close to the sun nor too far from its warmth. We propose that the 'Goldilocks Zone' also offers an apt metaphor for the struggle that people face when deciding if and when to consult a health care provider with a possible health problem. Drawing on decades of research in Denmark, England and Sweden on people's accounts of their experiences of accessing health care, this essay considers the ambivalence of health care seeking that individuals face in identifying when it is 'just right' to consult a general practitioner and the steps that health systems and individual clinicians might take to widen the zone.
|
|
