DNA replication and genome stability
TalTech priority area
Research classification (Frascati)
Head of the research group
Doctoral students
Keyword
DNA replication
replisome
origin firing
cell biology
molecular biology
DNA damage signaling
Overview
DNA replication is an essential process of genome duplication that has to be tightly regulated to ensure that each part of the genome isduplicated once and only once per cell cycle. DNAreplication remains one of the main targets ofcancer therapies as cancer cells tend to proliferate faster and are generally prone to replicationstress. One way to make replication targetingdrugs more efficient is to increase the number ofreplication forks in cancer cells. However, mostof the replication initiation research to date hasbeen done using model organisms such as yeastSaccharomyces cerevisiae and Saccharomycespombe, or Xenopus laevis egg extracts. The human DNA replication system is, as expected,much more complex, and identifying humanhomologs using data from model systems hasproven difficult, resulting in the need to reevaluate every finding from a model system ona case-by-case basis.Currently the research is focused on the following topics: (1) the role of DNA polymerase epsilonin replication initiation in human cells; (2) developing a novel system to study DNA replicationinitiation in human cells based on proximitylabelling; (3) the role and order of kinase activities in replication initiation.
Related projects
Related department
Department of chemistry and biotechnology
Teadusgrupiga seotud publikatsioonid
- Vipat, S., Gupta, D., Jonchhe, S., Anderspuk, H., Rothenberg, E., Moiseeva, T. N. The non-catalytic role of DNA polymerase epsilon in replication initiation in human cells // Nature communications (2022) vol. 13, art. 7099.
https://doi.org/10.1038/s41467-022-34911-4 - Sugitani, N., Vendetti, F.P., Cipriano, A.J., Deppas, J.J., Moiseeva, T.N., Schamus-Haynes, S., Wang, Y., Palmer, D., Osmanbeyoglu, H.U., Bostwick, A., Snyder, N.W., Gong, Y., Aird, K.M., Delgoffe, G.M., Beumer, J.H., Bakkenis, C.J. ATR kinase inhibition induces thymineless death in proliferating CD8+ T cells // bioRxiv (2022)
https://doi.org/10.1101/2022.02.24.481821 - Sugitani, N., Vendetti, F. P., Cipriano, A. J., Pandya, P., Deppas, J. J., Moiseeva, T. N., Schamus-Haynes, S., Wang, Y., Palmer, D., Osmanbeyoglu, H. U. et al. Thymidine rescues ATR kinase inhibitor-induced deoxyuridine contamination in genomic DNA, cell death, and interferon-α/β expression // The Cell Reports (2022) vol. 40, 12, art. 111371.
https://doi.org/10.1016/j.celrep.2022.111371 - Moiseeva, T.N., Qian, C., Sugitani, N., Osmanbeyoglu, H.U., Bakkenist, C.J. WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- And S-phase cells // Proceedings of the National Academy of Sciences of the United States of America (2019) vol. 116, 48, 3 p. : ill.
https://doi.org/10.1073/pnas.1915108116 - Ashton, N. W., Prakash, A., Moiseeva, T. N. Editorial : regulatory networks in genome stability pathways // Frontiers in Genetics (2023) vol. 14
https://doi.org/10.3389/fgene.2023.1171136