Rob de Bruin Research Group

1997 - M.S. Vrije Universiteit, Amsterdam, the Netherlands.
2002 - Ph.D. Vrije Universiteit, Amsterdam, the Netherlands.
Rob de Bruin
Tel: 020 7679 7255
Fax: 020 7679 7805
AAAS/Science Program for Excellence in Science 2007.
MRC Career Development Award 2009.
CRUK Programme Foundation award 2015
Previous Posts: 
2002 - Postdoctoral Fellow, The Scripps Research Institute, San Diego, USA. 

2009 - Group leader, MRC Laboratory for Molecular Cell Biology, London, UK


The work in the lab focuses on two
main lines of investigation.


Elucidating the mechanism and functional importance of the regulation of the
cell cycle transcriptional program by the checkpoints that ensure the
maintenance of genome integrity.


Obtaining a better understanding of fundamental
regulatory pathways that cause changes in cell-cycle regulated gene expression
and the importance of this regulation for the maintenance of genome


work is aimed at helping explain, at the molecular level, why defects in
proteins ranging from gene-specific transcriptional regulators to global
regulators of transcription are associated with human disease most notably


Cell cycle regulated transcription and control of
genome integrity.

starts with one cell, a fertilized egg. This one cell will multiply, through
cell division, and change into all the different cells needed to make a whole,
complicated organism such as a human being. This astonishing process requires
tight control of all cell divisions taking place during development and
throughout the life of for example a human being. This regulation is controlled
by several ‘cell cycle checkpoints’ that ensure no mistakes are made before a
cell is allowed to progress through the cell cycle in order to divide.

is a group of diseases in which cells
continue to multiply in an unregulated manner as a result of
checkpoint failure. Initiation of the cell division
cycle in human cells is imposed during the G1-phase of the cell cycle.
Activation of a large group of cell cycle dependent transcripts in G1 drives
entry into the next phase of the cell cycle, S phase, and thereby committing
cells to a new cell division cycle. The high frequency of genetic alterations
that affect proteins involved in G1/S transcriptional regulation detected in
human tumor cells illustrates the importance of this regulation for faithful
cell proliferation.

Molecular Cell Cover 18th August.jpg

Yeast as a model for human cells,
human cells as a model for cancer.

utilize the model organisms budding yeast, Saccharomyces
and the distantly related fission yeast, Schizosaccharomyces pombe, to identify
basic molecular mechanisms involved in transcriptional regulation during the
cell-cycle and in response to genotoxic stress. In addition, using the insight
obtained from past and ongoing work in yeast as a guide, we direct efforts to
elucidate the mechanism and functional importance of this regulation in human


The role of E2F activity in
oncogene-induced replication stress.

such as Ras, c-myc and CyclinE, deregulate E2F-dependent G1/S transcription to
drive passage into S-phase and cell proliferation. By accelerating S-phase
entry, these oncogenes also generate replication stress a crucial driver of genomic
instability and one of the key events
contributing to the onset of cancer. Whilst this suggests a direct link between
E2F deregulation and oncogene-induced replication stress, our
recent work indicates that cells experiencing replication stress also rely on
E2F-dependent transcription to prevent replication stress-induced DNA damage. Based on our findings we propose a model in which cells that experience
oncogene-induced replication stress become addicted to E2F activity to cope with high levels of replication stress, exposing a potential
therapeutic window to target specific cancer cells.


Exploit cancer’s addiction to
deregulated G1/S transcription.

The overall aim of our work our CRUK funded work is to provide a comprehensive
understanding of the role of E2F-dependent transcription in the underlying
mechanism of oncogene-induced replication stress and tolerance.
The correlation between E2F deregulation and replication stress during oncogene
transformation might provide clear markers for tumor progression and
intra-tumor heterogeneity. This could guide the best treatment strategy based
on specific deregulation of replication-initiation. Identification of E2F
target proteins involved in replication stress tolerance will provide potential
anti-cancer drug targets. Inactivation of these proteins is expected to affect
the protective buffer of cancer cells with high levels of replication stress.
In conclusion a detailed understanding
of the role of E2F-dependent transcription in oncogene-induced replication
stress provides
novel therapeutic approaches that will translate into significant benefits for
cancer patients and their families.

Lab Members: 
Cosetta Bertoli
PhD Student
Anna Herlihy
Anastasiya Kishkevich
Jump to: 2014 | 2013 | 2012 | 2011 | 2009 | 2008 | 2007 | 2006 | 2004 | 2001 | 2000 | 1999 | 1998 | 1997
Number of items: 29.


Bertoli, C; De Bruin, RAM; (2014) Turning cell cycle entry on its head: New data on the relationship between two proteins, cyclin d and rb, suggest that we need to re-evaluate our understanding of how cells enter into the cell cycle. eLife , 2014 (3) 10.7554/eLife.03475.

Caetano, C; Limbo, O; Farmer, S; Klier, S; Dovey, C; Russell, P; de Bruin, RA; (2014) Tolerance of Deregulated G1/S Transcription Depends on Critical G1/S Regulon Genes to Prevent Catastrophic Genome Instability. Cell Rep , 9 (6) pp. 2279-2289. 10.1016/j.celrep.2014.11.039. Green open access

De Bruin, RAM; (2014) Science of the cell cycle. International Innovation (147) pp. 68-70. Green open access

Klier, S; Farmer, S; de Bruin, RA; (2014) Analyzing G1-S transcriptional control. Methods Mol Biol , 1170 pp. 463-476. 10.1007/978-1-4939-0888-2_25.


Bertoli, C; Klier, S; McGowan, C; Wittenberg, C; de Bruin, RA; (2013) Chk1 inhibits E2F6 repressor function in response to replication stress to maintain cell-cycle transcription. Curr Biol , 23 (17) pp. 1629-1637. 10.1016/j.cub.2013.06.063.

Bertoli, C; Skotheim, JM; de Bruin, RA; (2013) Control of cell cycle transcription during G1 and S phases. Nat Rev Mol Cell Biol , 14 (8) pp. 518-528. 10.1038/nrm3629.

Harris, MR; Lee, D; Farmer, S; Lowndes, NF; de Bruin, RA; (2013) Binding specificity of the G1/S transcriptional regulators in budding yeast. PLoS One , 8 (4) , Article e61059. 10.1371/journal.pone.0061059. Green open access

Pereira Fraga Caetano, CM; (2013) G1/S Cell Cycle Regulated Transcription and Genome Stability. Doctoral thesis, UCL (University College London). Green open access

Travesa, A; Kalashnikova, TI; de Bruin, RA; Cass, SR; Chahwan, C; Lee, DE; Lowndes, NF; (2013) Repression of G1/S transcription is mediated via interaction of the GTB motifs of Nrm1 and Whi5 with Swi6. Mol Cell Biol , 33 (8) pp. 1476-1486. 10.1128/MCB.01333-12.


Bastos de Oliveira, FM; Harris, MR; Brazauskas, P; de Bruin, RA; Smolka, MB; (2012) Linking DNA replication checkpoint to MBF cell-cycle transcription reveals a distinct class of G1/S genes. EMBO J , 31 (7) pp. 1798-1810. 10.1038/emboj.2012.27.

Smolka, MB; Bastos de Oliveira, FM; Harris, MR; de Bruin, RA; (2012) The checkpoint transcriptional response: make sure to turn it off once you are satisfied. Cell Cycle , 11 (17) pp. 3166-3174. 10.4161/cc.21197.

Travesa, A; Kuo, D; de Bruin, RA; Kalashnikova, TI; Guaderrama, M; Thai, K; Aslanian, A; (2012) DNA replication stress differentially regulates G1/S genes via Rad53-dependent inactivation of Nrm1. EMBO J , 31 (7) pp. 1811-1822. 10.1038/emboj.2012.28.


Caetano, C; Klier, S; de Bruin, RAM; (2011) Phosphorylation of the MBF Repressor Yox1p by the DNA Replication Checkpoint Keeps the G1/S Cell-Cycle Transcriptional Program Active. PLOS ONE , 6 (2) , Article e17211. 10.1371/journal.pone.0017211. Green open access


Aligianni, S; Lackner, DH; Klier, S; Rustici, G; Wilhelm, BT; Marguerat, S; Codlin, S; (2009) The Fission Yeast Homeodomain Protein Yox1p Binds to MBF and Confines MBF-Dependent Cell-Cycle Transcription to G1-S via Negative Feedback. PLoS Genetics , 5 (8) , Article e1000626. 10.1371/journal.pgen.1000626. Green open access

Wagner, MV; Smolka, MB; de Bruin, RAM; Zhou, HL; Wittenberg, C; Dowdy, SF; (2009) Whi5 Regulation by Site Specific CDK-Phosphorylation in Saccharomyces cerevisiae. PLOS ONE , 4 (1) , Article e4300. 10.1371/journal.pone.0004300. Green open access

de Bruin, RAM; Wittenberg, C; (2009) All eukaryotes: Before turning off G(1)-S transcription, please check your DNA. CELL CYCLE , 8 (2) 214 - 217.


Ashe, M; de Bruin, RAM; Kalashnikova, T; McDonald, WH; Yates, JR; Wittenberg, C; (2008) The SBF- and MBF-associated protein Msa1 is required for proper timing of G(1)-specific transcription in Saccharomyces cerevisiae. J BIOL CHEM , 283 (10) 6040 - 6049. 10.1074/jbc.M708248200. Gold open access

Souer, E; Rebocho, AB; Bliek, M; Kusters, E; de Bruin, RAM; Koes, R; (2008) Patterning of inflorescences and flowers by the F-box protein DOUBLE TOP and the LEAFY homolog ABERRANT LEAF AND FLOWER of petunia. PLANT CELL , 20 (8) 2033 - 2048. 10.1105/tpc.108.060871.

de Bruin, RAM; Kalashnikova, TI; Aslanian, A; Wohischlegel, J; Chahwan, C; Yates, JR; Russell, P; (2008) DNA replication checkpoint promotes G(1)-S transcription by inactivating the MBF repressor Nrm1. P NATL ACAD SCI USA , 105 (32) 11230 - 11235. 10.1073/pnas.0801106105.

de Bruin, RAM; Kalashnikova, TI; Wittenberg, C; (2008) Stb1 Collaborates with Other Regulators To Modulate the G(1)-Specific Transcriptional Circuit. MOL CELL BIOL , 28 (22) 6919 - 6928. 10.1128/MCB.00211-08.


Limbo, O; Chahwan, C; Yamada, Y; de Bruin, RAM; Wittenberg, C; Russell, P; (2007) Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control double-strand break repair by homologous recombination. MOL CELL , 28 (1) 134 - 146. 10.1016/j.molcel.2007.09.009.


de Bruin, RAM; Kalashnikova, TI; Chahwan, C; McDonald, WH; Wohlschlegel, J; Yates, J; Russell, P; (2006) Constraining G1-specific transcription to late G1 phase: The MBF-associated corepressor Nrm1 acts via negative feedback. MOL CELL , 23 (4) 483 - 496. 10.1016/j.molcel.2006.06.025.


de Bruin, RAM; McDonald, WH; Kalashnikova, TI; Yates, J; Wittenberg, C; (2004) Cln3 activates G1-specific transcription via phosphorylation of the SBF transcription bound repressor Whi5. CELL , 117 (7) 887 - 898.


Johnsson, A; Byrne, P; de Bruin, R; Weiner, D; Wong, J; Los, G; (2001) Identification of gene clusters differentially expressed during the cellular injury responses (CIR) to cisplatin. Br J Cancer , 85 (8) pp. 1206-1210. 10.1054/bjoc.2001.2080.


Stam, M; de Bruin, R; van Blokland, R; van der Hoorn, RA; Mol, JN; Kooter, JM; (2000) Distinct features of post-transcriptional gene silencing by antisense transgenes in single copy and inverted T-DNA repeat loci. Plant J , 21 (1) pp. 27-42.


de Bruin, R; Spelt, K; Mol, J; Koes, R; Quattrocchio, F; (1999) Selection of high-affinity phage antibodies from phage display libraries. Nat Biotechnol , 17 (4) pp. 397-399. 10.1038/7959.


De Las Alas, MM; De Bruin, RAM; Ten Eyck, L; Los, G; Howell, SB; (1998) Prediction-based threading of the hMSH2 DNA mismatch repair protein. FASEB J , 12 (9) 653 - 663.

de las Alas, MM; de Bruin, RAM; Ten Eyck, L; Los, G; Howell, SB; (1998) Generating a theoretical model of the DNA mismatch repair protein hMSH2 using prediction-based threading. J MOL GRAPH MODEL , 16 (4-6) 286 - 286.


Stam, M; De Bruin, R; Kenter, S; Van der Hoorn, RAL; Van Blokland, R; Mol, JNM; Kooter, JM; (1997) Post-transcriptional silencing of chalcone synthase in petunia by inverted transgene repeats. Plant Journal , 12 (1) pp. 63-82.

This list was generated on Sun Nov 22 11:42:53 2015 GMT.