ATM/Wip1 Activities at Chromatin Control Plk1 Re-activation to Determine G2 Checkpoint Duration

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2017 Jun 14

PMID 28607002

Citations 23

Authors

Himjyot Jaiswal

Jan Benada

Erik Mullers

Karen Akopyan

Kamila Burdova

Tobias Koolmeister

Thomas Helleday

Rene H Medema

Libor Macurek

Arne Lindqvist

Affiliations

Soon will be listed here.

Abstract

After DNA damage, the cell cycle is arrested to avoid propagation of mutations. Arrest in G2 phase is initiated by ATM-/ATR-dependent signaling that inhibits mitosis-promoting kinases such as Plk1. At the same time, Plk1 can counteract ATR-dependent signaling and is required for eventual resumption of the cell cycle. However, what determines when Plk1 activity can resume remains unclear. Here, we use FRET-based reporters to show that a global spread of ATM activity on chromatin and phosphorylation of ATM targets including KAP1 control Plk1 re-activation. These phosphorylations are rapidly counteracted by the chromatin-bound phosphatase Wip1, allowing cell cycle restart despite persistent ATM activity present at DNA lesions. Combining experimental data and mathematical modeling, we propose a model for how the minimal duration of cell cycle arrest is controlled. Our model shows how cell cycle restart can occur before completion of DNA repair and suggests a mechanism for checkpoint adaptation in human cells.

Citing Articles

PPM1D activity promotes cellular transformation by preventing senescence and cell death.

Stoyanov M, Martinikova A, Matejkova K, Horackova K, Zemankova P, Burdova K Oncogene. 2024; 43(42):3081-3093.

PMID: 39237765 PMC: 11473410. DOI: 10.1038/s41388-024-03149-3.

The expression and clinical significance of PLK1/p-PLK1 protein in NK/T cell Lymphoma.

Zhang Z, Liu E, Zhang D, Zhao W, Wang G, Zhang Y Diagn Pathol. 2023; 18(1):129.

PMID: 38037110 PMC: 10691161. DOI: 10.1186/s13000-023-01413-w.

SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response.

Bland P, Saville H, Wai P, Curnow L, Muirhead G, Nieminuszczy J Nat Genet. 2023; 55(8):1311-1323.

PMID: 37524790 PMC: 10412459. DOI: 10.1038/s41588-023-01460-5.

PPM1D activity promotes the replication stress caused by cyclin E1 overexpression.

Martinikova A, Stoyanov M, Oravetzova A, Kok Y, Yu S, Dobrovolna J Mol Oncol. 2023; 18(1):6-20.

PMID: 37067201 PMC: 10766204. DOI: 10.1002/1878-0261.13433.

ATM-SPARK: A GFP phase separation-based activity reporter of ATM.

Li X, Chung C, Yang J, Chaudhuri S, Munster P, Shu X Sci Adv. 2023; 9(9):eade3760.

PMID: 36857446 PMC: 9977181. DOI: 10.1126/sciadv.ade3760.

References

Reinhardt H, Yaffe M . Kinases that control the cell cycle in response to DNA damage: Chk1, Chk2, and MK2. Curr Opin Cell Biol. 2009; 21(2):245-55. PMC: 2699687. DOI: 10.1016/j.ceb.2009.01.018. View

Lindqvist A, de Bruijn M, Macurek L, Bras A, Mensinga A, Bruinsma W . Wip1 confers G2 checkpoint recovery competence by counteracting p53-dependent transcriptional repression. EMBO J. 2009; 28(20):3196-206. PMC: 2771084. DOI: 10.1038/emboj.2009.246. View

Durocher D, Taylor I, Sarbassova D, Haire L, Westcott S, Jackson S . The molecular basis of FHA domain:phosphopeptide binding specificity and implications for phospho-dependent signaling mechanisms. Mol Cell. 2000; 6(5):1169-82. DOI: 10.1016/s1097-2765(00)00114-3. View

Mu J, Wang Y, Luo H, Leng M, Zhang J, Yang T . A proteomic analysis of ataxia telangiectasia-mutated (ATM)/ATM-Rad3-related (ATR) substrates identifies the ubiquitin-proteasome system as a regulator for DNA damage checkpoints. J Biol Chem. 2007; 282(24):17330-4. DOI: 10.1074/jbc.C700079200. View

Liang H, Esposito A, De S, Ber S, Collin P, Surana U . Homeostatic control of polo-like kinase-1 engenders non-genetic heterogeneity in G2 checkpoint fidelity and timing. Nat Commun. 2014; 5:4048. PMC: 4059941. DOI: 10.1038/ncomms5048. View

Wang L, Guo Q, Fisher L, Liu D, Peng A . Regulation of polo-like kinase 1 by DNA damage and PP2A/B55α. Cell Cycle. 2014; 14(1):157-66. PMC: 4615057. DOI: 10.4161/15384101.2014.986392. View

Macurek L, Lindqvist A, Lim D, Lampson M, Klompmaker R, Freire R . Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery. Nature. 2008; 455(7209):119-23. DOI: 10.1038/nature07185. View

Jaiswal H, Benada J, Mullers E, Akopyan K, Burdova K, Koolmeister T . ATM/Wip1 activities at chromatin control Plk1 re-activation to determine G2 checkpoint duration. EMBO J. 2017; 36(14):2161-2176. PMC: 5510006. DOI: 10.15252/embj.201696082. View

Tkacz-Stachowska K, Lund-Andersen C, Velissarou A, Myklebust J, Stokke T, Syljuasen R . The amount of DNA damage needed to activate the radiation-induced G2 checkpoint varies between single cells. Radiother Oncol. 2011; 101(1):24-7. DOI: 10.1016/j.radonc.2011.05.060. View

10.

Peng C, Graves P, Thoma R, Wu Z, Shaw A, Piwnica-Worms H . Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science. 1997; 277(5331):1501-5. DOI: 10.1126/science.277.5331.1501. View

11.

Reinhardt H, Hasskamp P, Schmedding I, Morandell S, van Vugt M, Wang X . DNA damage activates a spatially distinct late cytoplasmic cell-cycle checkpoint network controlled by MK2-mediated RNA stabilization. Mol Cell. 2010; 40(1):34-49. PMC: 3030122. DOI: 10.1016/j.molcel.2010.09.018. View

12.

Krenning L, Feringa F, Shaltiel I, van den Berg J, Medema R . Transient activation of p53 in G2 phase is sufficient to induce senescence. Mol Cell. 2014; 55(1):59-72. DOI: 10.1016/j.molcel.2014.05.007. View

13.

Li X, Lee Y, Jeng J, Yen Y, Schultz D, Shih H . Role for KAP1 serine 824 phosphorylation and sumoylation/desumoylation switch in regulating KAP1-mediated transcriptional repression. J Biol Chem. 2007; 282(50):36177-89. DOI: 10.1074/jbc.M706912200. View

14.

Syljuasen R, Jensen S, Bartek J, Lukas J . Adaptation to the ionizing radiation-induced G2 checkpoint occurs in human cells and depends on checkpoint kinase 1 and Polo-like kinase 1 kinases. Cancer Res. 2006; 66(21):10253-7. DOI: 10.1158/0008-5472.CAN-06-2144. View

15.

Peter M, Nakagawa J, Doree M, Labbe J, Nigg E . In vitro disassembly of the nuclear lamina and M phase-specific phosphorylation of lamins by cdc2 kinase. Cell. 1990; 61(4):591-602. DOI: 10.1016/0092-8674(90)90471-p. View

16.

Matsuoka S, Ballif B, Smogorzewska A, McDonald 3rd E, Hurov K, Luo J . ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007; 316(5828):1160-6. DOI: 10.1126/science.1140321. View

17.

Kim B, Li Y, Zhang J, Xi Y, Li Y, Yang T . Genome-wide reinforcement of cohesin binding at pre-existing cohesin sites in response to ionizing radiation in human cells. J Biol Chem. 2010; 285(30):22784-92. PMC: 2906269. DOI: 10.1074/jbc.M110.134577. View

18.

Rauta J, Alarmo E, Kauraniemi P, Karhu R, Kuukasjarvi T, Kallioniemi A . The serine-threonine protein phosphatase PPM1D is frequently activated through amplification in aggressive primary breast tumours. Breast Cancer Res Treat. 2005; 95(3):257-63. DOI: 10.1007/s10549-005-9017-7. View

19.

Fuller B, Lampson M, Foley E, Rosasco-Nitcher S, Le K, Tobelmann P . Midzone activation of aurora B in anaphase produces an intracellular phosphorylation gradient. Nature. 2008; 453(7198):1132-6. PMC: 2724008. DOI: 10.1038/nature06923. View

20.

Mamely I, van Vugt M, Smits V, Semple J, Lemmens B, Perrakis A . Polo-like kinase-1 controls proteasome-dependent degradation of Claspin during checkpoint recovery. Curr Biol. 2006; 16(19):1950-5. DOI: 10.1016/j.cub.2006.08.026. View