Arne Lindqvist's Group
We are interested in how human cells decide to divide, the signalling regulating mitotic entry and its interplay with DNA-damage checkpoints.
Entry into mitosis is regulated by a complex signalling network, converging on activation of mitotic Cyclin-Cdk complexes. To prevent transmission of mutations, this network is strictly controlled by DNA-damage checkpoints. In fact, DNA-damage checkpoint signalling and mitotic entry signalling can both modify each other. Because of these modifications, the decision to enter mitosis is taken differently after recovery from a DNA-damage checkpoint compared to during unperturbed growth.
We focus on two main approaches to study the mitotic entry network and its interplay with DNA-damage checkpoints. First, we investigate the function and regulation of individual proteins involved in these processes. Second, we assemble experimentally derived biophysical models to study how these proteins function together. To support both of these approaches we also focus on developing novel microscopy-based techniques.
DNA Replication Determines Timing of Mitosis by Restricting CDK1 and PLK1 Activation.
Lemmens B, Hegarat N, Akopyan K, Sala-Gaston J, Bartek J, Hochegger H, et al
Mol. Cell 2018 07;71(1):117-128.e3
ATM/Wip1 activities at chromatin control Plk1 re-activation to determine G2 checkpoint duration.
Jaiswal H, Benada J, Müllers E, Akopyan K, Burdova K, Koolmeister T, et al
EMBO J. 2017 07;36(14):2161-2176
Residual Cdk1/2 activity after DNA damage promotes senescence.
Müllers E, Silva Cascales H, Burdova K, Macurek L, Lindqvist A
Aging Cell 2017 06;16(3):575-584
Nuclear translocation of Cyclin B1 marks the restriction point for terminal cell cycle exit in G2 phase.
Müllers E, Silva Cascales H, Jaiswal H, Saurin AT, Lindqvist A
Cell Cycle 2014 ;13(17):2733-43
Assessing kinetics from fixed cells reveals activation of the mitotic entry network at the S/G2 transition.
Akopyan K, Silva Cascales H, Hukasova E, Saurin AT, Müllers E, Jaiswal H, et al
Mol. Cell 2014 Mar;53(5):843-53