Hein te Riele

..They show that retinoblastoma is not driven by uncontrolled expansion of retinal progenitor cells, but rather is the result of cell cycle re-entry and expansion of differentiated horizontal interneurons in the retina...

..Here, we discuss the similarities and differences between these restriction points and the roles of cyclin-dependent kinase inhibitors (CKIs) herein...

..In this issue of Cell Stem Cell, Liu et al. (2009) demonstrate that a similar transition can be achieved by culturing retinoblastoma-deficient mouse embryonic fibroblasts in suspension...

..We have used this method to create a codon substitution (N750F) in the Rb gene of mouse ES cells and show that the oligonucleotide-modified Rb allele can be transmitted through the germ line of mice...

..Thus, transient MLH1 suppression provides a valuable extension of the MSH2 knockdown strategy, allowing rapid generation of mice carrying single basepair alterations in their genome...

..This suggests that the spindle checkpoint blocks D box recognition of APC/C-bound cyclin B1, whereas distinctive complexes between the N terminus of cyclin A and Cdc20 evade checkpoint control...

..In addition, we were not able to derive cisplatin-resistant subclones from this freshly generated MMR-deficient cell line. Thus, in ES cells we did not find evidence for direct involvement of MMR deficiency in cisplatin resistance...

..The lack of an augmented phenotype suggest that null mutations in Fanca or Fancg are fully epistatic, making additional important functions outside of the FA core complex highly unlikely...

..The involvement of p53 provides a rationale for the synergism between loss of Rb and p53 in tumorigenesis...

..The ability of ES cells to differentiate into various cell types after ssODN-mediated gene targeting may offer opportunities for future therapeutic applications...

..This mechanism may allow premalignant tumor cells to acquire additional genetic alterations that promote tumorigenesis...

..Since transformation of human fibroblasts also requires ablation of both pathways, our results imply that the mechanisms underlying transformation of human and mouse cells are not as different as previously claimed...

..The FA-M mouse model presented here suggests that FANCM functions both inside and outside the FA core complex to maintain genome stability and to prevent tumorigenesis...

..These results indicate that the G2 restriction point does operate in vivo. However, in the pituitary gland, this mechanism seems to retard rather than to prevent tumor growth...

..Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd...

..Thus, progression to malignancy of Rb-deficient lesions by alleviation of G2 arrest may offer an alternative explanation for the synergism between loss of Rb and p53 in tumorigenesis...

..The redundancy of the retinoblastoma proteins in vivo is reflected by the behavior of Rb-family-defective mouse embryonic fibroblasts in vitro...

..Mutation analysis of ENU-induced Hprt mutants revealed that base substitutions occurred predominantly at A-T base-pairs. These results suggest that MMR modulates the processing of ethylation damage at AT base-pairs...

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..We show that PCR-based procedures can be used to identify and clone modified cells. By this method we have substituted a single codon in the retinoblastoma gene...

..Our results highlight the important differences that exist in tumor susceptibility between mice and man (e.g pineal gland) and question the photoreceptor cell origin of human retinoblastoma...

..We have also shown that oligonucleotide-directed gene modification provides a straightforward approach to recreate allelic variants in the endogenous gene in murine ESC. This approach can be extended to other hereditary conditions...

..Here we summarize the current knowledge on the retinoblastoma protein in fat cells, with particular emphasis on its potential role in adipocyte lineage commitment and differentiation...

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..We propose that pRB acts as a molecular switch determining white vs. brown adipogenesis, suggesting a previously uncharacterized function of this key cell cycle regulator in adipocyte lineage commitment and differentiation...