How do cells finish genome replication?
How do cells finish genome replication?
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Each time a cell divides, it has to replicate all of its DNA. In human cells, this is about 6.4 billion base pairs! Our textbooks have taught us that this takes place in the S phase of the cell cycle, and then during Mitosis, a cell splits into two cells, each with a full genome. But it turns out that cells can and frequently do synthesize DNA during Mitosis. How do cells finish replicating their genomes during Mitosis?
What does DNA synthesis "look" like during Mitosis?
What does DNA synthesis "look" like during Mitosis?
Mitosis is a very different environment than S phase. How does this impact the DNA replication machinery? How does this impact the structure of the DNA being replicated? And what is the outcome - how do cells make sure their genomes are faithfully duplicated with this mitotic-style replication?
Our tools
Our tools
We use the versatile and powerful biochemical reconstitution of DNA replication as our main tool, and we complement it with the classic power of yeast genetics. These two approaches inform one another and help us think about both fine mechanistic details as well as integrating our ideas in a physiological context.
Beyond the mechanism
Beyond the mechanism
Understanding how mitotic DNA synthesis works in a biochemical reaction and in yeast cells is really cool! But also, these mechanistic insights create a framework so that we can ask the right questions in mammalian cells, cancer cells, and humans. DNA replication is a highly conserved process, and many of the genes involved in DNA replication are misregulated in tumors. Therefore, this work can also help us understand what goes wrong in cancer cells and inform treatments.
Allie's Publications (Allison W McClure)
Allie's Publications (Allison W McClure)
McClure, A.W.*, Canal, B.*, Diffley, J.F.X. (2022). DNA replication fork-centric view of the budding yeast DNA damage response. DNA Repair. PMID: 36108423.
McClure, A.W., and Diffley, J.F.X. (2021). Rad53 checkpoint kinase regulation of DNA replication fork rate via Mrc1 phosphorylation. Elife 10, 1-24. PMID: 34387546
Canal, B.*, McClure, A.W.*, Curran, J.F.*, Wu, M., Ulferts, R., Weissmann, F., Zeng, J., Bertolin, A.P., Milligan, J.C., Basu, S., Drury, L.S., Deegan, T.D., Fujisawa, R., Roberts, E.L., Basier, C., Labib, K., Beale, R., Howell, M., Diffley, J.F.X. (2021). Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp14/nsp10 exoribonuclease. Biochem. J. 478, 2445–2464. PMID: 34198326
Canal, B.*, Fujisawa, R.*, McClure, A.W.*, Deegan, T.D.*, Wu, M., Ulferts, R., Weissmann, F., Drury, L.S., Bertolin, A.P., Zeng, J., Beale, R., Howell, M., Labib, K., Diffley, J.F.X. (2021). Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp15 endoribonuclease. Biochem. J. 478, 2465–2479. PMID: 34198324
Basu, S.*, Mak, T.*, Ulferts, R., Wu, M., Deegan, T., Fujisawa, R., Tan, K.W., Lim, C.T., Basier, C., Canal, B., Curran, J.F., Drury, L.S., McClure, A.W., Roberts, E.L., Weissmann, F., Zeisner, T.U., Beale, R., Cowling, V.H., Howell, M., Labib, K., Diffley, J.F.X. (2021). Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of Nsp14 RNA cap methyltransferase. Biochem. J. 478, 2481–2497. PMID: 34198328
McClure, A.W., Jacobs, K.C., Zyla, T.R., and Lew, D.J. (2018). Mating in wild yeast: Delayed interest in sex after spore germination. Mol. Biol. Cell 29, 3119–3127. PMID: 30355051
McClure, A.W.*, Wu, C.-F.*, Johnson, S.A., and Lew, D.J. (2016). Imaging Polarization in Budding Yeast. Methods Mol. Biol. 1407, 13–23. PMID: 27271891
McClure, A.W.*, Minakova, M.*, Dyer, J.M.*, Zyla, T.R., Elston, T.C., and Lew, D.J. (2015). Role of Polarized G Protein Signaling in Tracking Pheromone Gradients. Dev. Cell. PMID: 26609960
McClure, A.W., and Lew, D.J. (2015). To avoid a mating mishap, yeast focus and communicate. J. Cell Biol. 208, 867–868.PMID: 25825514
McClure, A.W., and Lew, D.J. (2014). Cell Polarity: Netrin Calms an Excitable System. Curr. Biol. 24, R1050–R1052. PMID: 25517371
Howell, A.S., Savage, N.S., Johnson, S.A., Bose, I., Wagner, A.W., Zyla, T.R., Nijhout, H.F., Reed, M.C., Goryachev, A.B., and Lew, D.J. (2009). Singularity in polarization: rewiring yeast cells to make two buds. Cell 139, 731–743. PMID: 19914166
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