Hein te Riele
University of Amsterdam
Publications 17
#1Henri J. van de Vrugt (UvA: University of Amsterdam)H-Index: 1
#2Tim Harmsen (NKI-AVL: Netherlands Cancer Institute)H-Index: 2
Last.Hein te Riele (UvA: University of Amsterdam)H-Index: 13
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Fanconi anemia (FA) is a cancer predisposition syndrome characterized by congenital abnormalities, bone marrow failure, and hypersensitivity to aldehydes and crosslinking agents. For FA patients, gene editing holds promise for therapeutic applications aimed at functionally restoring mutated genes in hematopoietic stem cells. However, intrinsic FA DNA repair defects may obstruct gene editing feasibility. Here, we report on the CRISPR/Cas9-mediated correction of a disruptive mutation in Fancf. Our...
1 CitationsSource
#1Wouter van ZonH-Index: 8
#2Janneke OginkH-Index: 5
Last.Rob M. F. WolthuisH-Index: 18
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The ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) is activated at prometaphase by mitotic phosphorylation and binding of its activator, Cdc20. This initiates cyclin A degradation, whereas cyclin B1 is stabilized by the spindle checkpoint. Upon checkpoint release, the RXXL destruction box (D box) was proposed to direct cyclin B1 to core APC/C or Cdc20. In this study, we report that endogenous cyclin B1–Cdk1 is recruited to checkpoint-inhibited, phosphorylated APC/C in prometaphase...
35 CitationsSource
#1Tanja van HarnH-Index: 1
#2Floris Foijer (Wellcome Trust Sanger Institute)H-Index: 15
Last.Hein te RieleH-Index: 13
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Loss of G1/S control is a hallmark of cancer, and is often caused by inactivation of the retinoblastoma pathway. However, mouse embryonic fibroblasts lacking the retinoblastoma genes RB1, p107, and p130 (TKO MEFs) are still subject to cell cycle control: Upon mitogen deprivation, they enter and complete S phase, but then firmly arrest in G2. We now show that G2-arrested TKO MEFs have accumulated DNA damage. Upon mitogen readdition, cells resume proliferation, although only part of the damage is ...
89 CitationsSource
#1Tinke L. Vormer (NKI-AVL: Netherlands Cancer Institute)H-Index: 2
#2Floris Foijer (NKI-AVL: Netherlands Cancer Institute)H-Index: 15
Last.Hein te RieleH-Index: 13
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Mouse embryonic fibroblasts (MEFs) deficient for pocket proteins (i.e., pRB/p107-, pRB/p130-, or pRB/p107/p130-deficient MEFs) have lost proper G1 control and are refractory to RasV12-induced senescence. However, pocket protein-deficient MEFs expressing RasV12 were unable to exhibit anchorage-independent growth or to form tumors in nude mice. We show that depending on the level of pocket proteins, loss of adhesion induces G1 and G2 arrest, which could be alleviated by overexpression of the TBX2 ...
13 CitationsSource
#1Floris Foijer (D.A.R.E.: Drug Abuse Resistance Education)H-Index: 15
Last.Hein te RieleH-Index: 13
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Loss of activity of the retinoblastoma pathway is a common event in human cancer. Mouse models have revealed that tumorigenesis by loss of Rb was accelerated by concomitant loss of the cell cycle inhibitor p27 KIP1 . This has been attributed to reduced apoptosis and weakening of the G 1 checkpoint. However, the role of p27 KIP1 in a recently identified G 2 restriction point may offer an alternative explanation for this synergy. Here, we have investigated the significance of the G 2 restriction p...
4 CitationsSource
#1Floris FoijerH-Index: 15
Last.Hein te RieleH-Index: 13
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2 CitationsSource
#1Marieke AartsH-Index: 7
#2Marleen DekkerH-Index: 12
Last.Hein te RieleH-Index: 13
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Oligonucleotide-mediated gene targeting is emerging as a powerful tool for the introduction of subtle gene modifications in mouse embryonic stem (ES) cells and the generation of mutant mice. However, its efficacy is strongly suppressed by DNA mismatch repair (MMR). Here we report a simple and rapid procedure for the generation of mouse mutants using transient down regulation of the central MMR protein MSH2 by RNA interference. We demonstrate that under this condition, unmodified single-stranded ...
49 CitationsSource
#2Leontine SchuijffH-Index: 2
Last.Hein te RieleH-Index: 13
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The retinoblastoma gene family consists of three genes: RB, p107, and p130. While loss of pRB causes retinoblastoma in humans and pituitary gland tumors in mice, tumorigenesis in other tissues may be suppressed by p107 and p130. To test this hypothesis, we have generated chimeric mice from embryonic stem cells carrying compound loss-of-function mutations in the Rb gene family. We found that Rb/p107- and Rb/p130-deficient mice were highly cancer prone. We conclude that in a variety of tissues tum...
107 CitationsSource
Adipocyte precursor cells give raise to two major cell populations with different physiological roles: white and brown adipocytes. Here we demonstrate that the retinoblastoma protein (pRB) regulates white vs. brown adipocyte differentiation. Functional inactivation of pRB in wild-type mouse embryo fibroblasts (MEFs) and white preadipocytes by expression of simian virus 40 large T antigen results in the expression of the brown fat-specific uncoupling protein 1 (UCP-1) in the adipose state. Retino...
243 CitationsSource
#1Nanna ClaijH-Index: 6
#2Anja van der WalH-Index: 8
Last.Hein te RieleH-Index: 13
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The primary role of the mismatch repair (MMR) system is the avoidance of mutations caused by replication and recombination errors. Furthermore, the lethality of methylating agents has been attributed to the processing of O 6 -methylguanine lesions in DNA by MMR. Loss of the MSH2 protein completely abolishes repair function and results in reduced cell killing by methylating agents and accelerated accumulation of methylation-damage-induced mutations. This has raised the question as to whether MMR ...
28 Citations