We are investigating the regulation of chromosomal DNA replication in eukaryotic cells. Our research focuses on the molecular mechanisms underlying the initiation step of DNA replication. In particular, we are interested to elucidate how initiation is regulated by the function of small non-coding RNAs such as Y RNAs and stem-bulge RNAs.
Current research topics include:
- Identifying replication proteins that bind specifically to non-coding Y RNAs – and characterising the functional relevance of these interactions for DNA replication;
- Identifying proteins that regulate, or overcome Y RNA function;
- Determining at nucleotide resolution the functional domains that are essential for Y RNA function during DNA replication;
- Identifying functional Y RNA homologues in non-vertebrate species to work out evolutionary conservation and history;
- Characterising interactions between Y RNAs and chromatin during DNA replication;
- Determining genome-wide specification and activation of human DNA replication origins.
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.
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.
Full list of publications available via PubMed