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Department of Zoology

 

Biography

I graduated with a degree in Biology and obtained my PhD at the University of Konstanz, Germany, having worked in the laboratory of Rolf Knippers on the assembly of nucleosomes during DNA replication. In 1994, I moved to Cambridge as a postdoc with an EMBO fellowship, working with Ron Laskey at the Wellcome/CRC Institute (now the Wellcome Trust/Cancer Research UK Gurdon Institute) on the regulation of human chromosomal DNA replication. I began to establish my own research group there from 1997 onwards as a Royal Society University Research Fellow. In 2000, I was appointed as a University Lecturer in Cell Biology and moved with my research group to the Department of Zoology.

Research

I am interested in the control of chromosomal DNA replication in eukaryotic cells. Current research in my group focuses on the initiation step of DNA replication, and in particular, how it is regulated by the function of small non-coding RNAs.

Before a cell can divide, it needs to replicate its chromosomal DNA. A key regulation step for the cell division cycle is the initiation of chromosomal DNA replication at the G1-to-S phase transition. We have established a cell-free system from human cells that reconstitutes this process in a test tube. We have used this experimental system to purify and to characterise essential initiation factors. We are currently focussing on the roles of small non-coding Y RNAs, which we have identified as essential initiation factors in vertebrate cells.

Our main research interest is the elucidation of molecular mechanisms by which the small non-coding Y RNAs exert their function during the initiation of DNA replication in vertebrate cells. We are also exploring the roles of functionally equivalent RNAs in other, non-vertebrate organisms.

Finally, we have recently begun to investigate the specification and activation of DNA replication origins on the human genome.

Publications

Key publications: 

Christov, C.P., Dingwell, K.S., Skehel, M., Wilkes, H.S., Sale, J.E., Smith, J.C., and Krude, T. (2018). A NuRD complex from Xenopus laevis eggs is essential for DNA replication during early embryogenesis. Cell Rep 22, 2265-2278. See https://www.zoo.cam.ac.uk/news/regulation-of-dna-replication-during-early-embryogenesis 

Kheir E. and Krude T. (2017). Non-coding Y RNAs associate with early replicating euchromatin in concordance with the origin recognition complex. J Cell Sci 130, 1239-50.

Langley A.R., Gräf S., Smith J.C. and Krude T. (2016). Genome-wide identification and characterisation of human DNA replication origins by initiation site sequencing (ini-seq). Nucleic Acids Res 44, 10230-47.

Kowalski M.P., Baylis H.A. and Krude T. (2015). Non-coding stem-bulge RNAs are required for cell proliferation and embryonic development in C. elegans. J Cell Sci 128, 2118-212.

Wang I., Kowalski M.P., Langley A.R., Rodriguez R., Balasubramanian S., Hsu S.T., Krude T. (2014). Nucleotide contributions to the structural integrity and DNA replication initiation activity of noncoding y RNA. Biochemistry 53, 5848-5863.

Collart, C., Christov, C.P., Smith, J.C., and Krude, T. (2011). The mid-blastula transition defines the onset of Y RNA-dependent DNA replication in Xenopus laevis. Mol Cell Biol 31, 3857-3870.

Zhang, A.T., Langley, A.R., Christov, C.P., Kheir, E., Shafee, T., Gardiner, T.J., and Krude, T. (2011). Dynamic interaction of Y RNAs with chromatin and initiation proteins during human DNA replication. J Cell Sci 124, 2058-2069.

Krude, T., Christov, C.P., Hyrien, O., and Marheineke, K. (2009). Y RNA functions at the initiation step of mammalian chromosomal DNA replication. J Cell Sci 122, 2836-2845.

Christov, C. P., Gardiner, T. J., Szüts, D., and Krude, T. (2006). Functional requirement of non-coding Y RNAs for human chromosomal DNA replication. Mol Cell Biol 26, 6993-7004.

Krude, T. (2000). Initiation of human DNA replication in vitro using nuclei from cells arrested at an initiation-competent state. J Biol Chem 275, 13699-13707.

Krude, T., Jackman, M., Pines, J., and Laskey, R.A. (1997). Cyclin/Cdk-dependent initiation of DNA replication in a human cell-free system. Cell 88, 109-119.

 

Other publications: 

Kowalski M.P. and Krude T. (2015). Functional roles of non-coding Y RNAs. Int J Biochem Cell Biol 66, 20-29.

Krude, T. (2010). Non-coding RNAs: New players in the field of eukaryotic DNA replication. Subcell Biochem 50, 105-118.

Langley, A.R., Chambers, H., Christov, C.P., and Krude, T. (2010). Ribonucleoprotein Particles Containing Non-Coding Y RNAs, Ro60, La and Nucleolin Are Not Required for Y RNA Function in DNA Replication. PLoS ONE 5, e13673.

Gardiner, T.J., Christov, C.P., Langley, A.R., and Krude, T. (2009). A conserved motif of vertebrate Y RNAs essential for chromosomal DNA replication. RNA 15, 1375-1385.

Christov, C.P., Trivier, E., and Krude, T. (2008). Noncoding human Y RNAs are overexpressed in tumours and required for cell proliferation. Br J Cancer 98, 981-988.

Klinge, S., Hirst, J., Maman, J. D., Krude, T., and Pellegrini, L. (2007). An iron-sulfur domain of the eukaryotic primase is essential for RNA primer synthesis. Nat Struct Mol Biol 14, 875-877.

Krude, T. (2006). Initiation of chromosomal DNA replication in mammalian cell-free systems. Cell Cycle 5, 2115-2122.

Nabatiyan, A., Szüts, D., and Krude, T. (2006). Induction of CAF-1 expression in response to DNA strand breaks in quiescent human cells. Mol Cell Biol 26, 1839-1849.

Marheineke, K., Hyrien, O., and Krude, T. (2005). Visualization of bidirectional initiation of chromosomal DNA replication in a human cell free system. Nucleic Acids Res 33, 6931-6941.

Szüts, D., Christov, C., Kitching, L., and Krude, T. (2005). Distinct populations of human PCNA are required for initiation of chromosomal DNA replication and concurrent DNA repair. Exp Cell Res 311, 240-250.

Szüts, D., and Krude, T. (2004). Cell cycle arrest at the initiation step of human chromosomal DNA replication causes DNA damage. J Cell Sci 117, 4897-4908.

Nabatiyan, A., and Krude, T. (2004). Silencing of Chromatin Assembly Factor 1 in human cells leads to cell death and loss of chromatin assembly during DNA synthesis. Mol Cell Biol 24, 2853-2862.

Szüts, D., Kitching, L., Christov, C., Budd, A., Peak-Chew, S., and Krude, T. (2003). RPA is an initiation factor for human chromosomal DNA replication. Nucleic Acids Res 31, 1725-1734.

Keller, C., Hyrien, O., Knippers, R., and Krude, T. (2002). Site-specific and temporally controlled initiation of DNA replication in a human cell-free system. Nucleic Acids Res30, 2114-2123.

Krude, T. (1999). Mimosine arrests proliferating human cells before onset of DNA replication in a dose-dependent manner. Exp Cell Res 247, 148-159.

Associate Professor

Contact Details

Room T1
01223 (3)30111
Accepting applications for PhD students.