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Department of Zoology


Fresh off the press:

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.

DNA replication in the embryo of Xenopus laevis changes dramatically at the mid-blastula transition (MBT), with Y RNA-independent random initiation switching to Y RNA-dependent initiation at specific origins. Here, we identify xNuRD, an MTA2-containing assemblage of the nucleosome remodelling and histone deacetylation complex NuRD, as an essential factor in pre-MBT Xenopus embryos that overcomes a functional requirement for Y RNAs during DNA replication. Human NuRD complexes have a different subunit composition from xNuRD, and do not support Y RNA-independent initiation of DNA replication. Blocking or immunodepletion of xNuRD inhibits DNA replication initiation in isolated nuclei in vitro, and causes inhibition of DNA synthesis, developmental delay and embryonic lethality in early embryos. xNuRD activity declines after the MBT, coinciding with dissociation of the complex and emergence of Y RNA-dependent initiation. Our data thus reveal an essential role for a NuRD complex as a DNA replication factor during early Xenopus development.  doi:10.1016/j.celrep.2018.02.015

Full publication list:

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Selected recent journal articles:

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, 1239-1250.

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, 10230–10247.

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, 2118-2129.

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

Wang, I., Kowalski, M.P., Langley, A.R., Rodriguez, R., Balasubramanian, S., Hsu, S.T., and 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. (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.

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., 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.

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. (2006).
Initiation of chromosomal DNA replication in mammalian cell-free systems. Cell Cycle 5, 2115-2122.
Click here for an open access to the pdf of this review

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 Res 30, 2114-2123.

Laman, H., Coverley, D., Krude, T., Laskey, R., and Jones, N. (2001).
Viral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication. Mol Cell Biol 21, 624-635.

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

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.




Krude, T., Editor (2003).
DNA: Changing Science and Society
Cambridge University Press,
200 pages,
ISBN 0521823781