Base excision repair (BER) is initiated by a DNA glycosylase and is completed by alternative routes, one of which requires proliferating cell nuclear antigen (PCNA) and other proteins also involved in DNA replication. We report that the major nuclear uracil-DNA glycosylase (UNG2) increases in S phase, during which it co-localizes with incorporated BrdUrd in replication foci. Uracil is rapidly removed from replicatively incorporated dUMP residues in isolated nuclei. Neutralizing antibodies to UNG2 inhibit this removal, indicating that UNG2 is the major uracil-DNA glycosylase responsible. PCNA and replication protein A (RPA) co-localize with UNG2 in replication foci, and a direct molecular interaction of UNG2 with PCNA (one binding site) and RPA (two binding sites) was demonstrated using two-hybrid assays, a peptide SPOT assay and enzyme-linked immunosorbent assays. These results demonstrate rapid post-replicative removal of incorporated uracil by UNG2 and indicate the formation of a BER complex that contains UNG2, RPA and PCNA close to the replication fork.

In the endeavour of biobank research there is dispute concerning what type of consent and which form of donor–biobank relationship meet high ethical standards. Up until now, a ‘broad consent' model has been used in many present-day biobank projects. However it has been, by some scholars, deemed as a pragmatic, and not an acceptable ethical solution. Calls for change have been made on the basis of avoidance of paternalism, intentions to fulfil the principle of autonomy, wish for increased user participation, a questioning of the role of experts and ideas advocating reduction of top–down governance. Recently, an approach termed ‘dynamic consent' has been proposed to meet such challenges. Dynamic consent uses modern communication strategies to inform, involve, offer choices and last but not the least obtain consent for every research projects based on biobank resources. At first glance dynamic consent seems appealing, and we have identified six claims of superiority of this model; claims pertaining to autonomy, information, increased engagement, control, social robustness and reciprocity. However, after closer examination, there seems to be several weaknesses with a dynamic consent approach; among others the risk of inviting people into the therapeutic misconception as well as individualizing the ethical review of research projects. When comparing the two models, broad consent still holds and can be deemed a good ethical solution for longitudinal biobank research. Nevertheless, there is potential for improvement in the broad model, and criticism can be met by adapting some of the modern communication strategies proposed in the dynamic consent approach.

In some families there is an increased risk for colorectal cancer, caused by heritable, but often unidentified genetic mutations predisposing to the disease. We have identified the likely genetic cause for disease predisposition in a large family with high burden of colorectal adenomas and carcinomas, in addition to extra-colonic cancers. This family had previously been tested for known cancer susceptibility genes, with negative results. Exome sequencing was used to identify a novel mutation, c.1373A>T (p.Tyr458Phe), in the gene for DNA polymerase epsilon catalytic subunit (POLE). This mutation is located in the active site of the exonuclease domain of the enzyme, and affects a residue that has previously been shown to be important for exonuclease activity. The first predisposing mutation identified in POLE (c.1270C>G, p.Leu424Val) was associated with colorectal cancer only, but another mutation with a broader tumour spectrum (c.1089C>A, p.Asn363Lys) has recently been reported. In the family described in the present study, carriers generally have multiple colorectal adenomas and cancer of colon, pancreas, ovaries and small intestine which represents an important broadening of the tumour spectrum of POLE mutation carriers. We also observe a large phenotypic variation among the POLE mutation carriers in this family, most likely explained by modifying variants in other genes. One POLE mutation carrier has a novel variant in EXO1 (c.458C>T, p.Ala153Val), which may contribute to a more severe phenotype. The findings in this study will have important implications for risk assessment and surveillance of POLE mutation carriers.Electronic supplementary materialThe online version of this article (doi:10.1007/s10689-015-9803-2) contains supplementary material, which is available to authorized users.

Great hope has been placed on biobank research as a strategy to improve diagnostics, therapeutics and prevention. It seems to be a common opinion that these goals cannot be reached without the participation of commercial actors. However, commercial use of biobanks is considered morally problematic and the commercialisation of human biological materials is regulated internationally by policy documents, conventions and laws. For instance, the Council of Europe recommends that: “Biological materials should not, as such, give rise to financial gain”. Similarly, Norwegian legislation reads: “Commercial exploitation of research participants, human biological material and personal health data in general is prohibited”. Both articles represent kinds of common moral intuitions. A problem, however, is that legislative documents are too vague and provide room for ample speculation. Through the use of focus group interviews with Norwegian biobank donors, we have tried to identify lay intuitions and morals regarding the commercial use of biobanks. Our findings indicate that the act of donation and the subsequent uses of the samples belong to two different spheres. While concerns around dignity and commodification were present in the first, injustice and unfairness were our informants’ major moral concerns in the latter. Although some opposition towards commercial actors was voiced, these intuitions show that it is possible to render commercial use of biobanks ethically acceptable based on frameworks and regulations which hinder commodification of the human body and promote communal benefit sharing.

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