Jiri Bartek group
Cells employ an extensive network of DNA damage response (DDR) processes to maintain genome integrity and to promote survival after exposure to genotoxic stresses. Distinct DNA repair pathways respond to different types of damage, while cell cycle checkpoints provide the time that is needed to repair DNA lesions. Research in the Bartek lab focuses on various mechanistic aspects of the DDR and DNA repair pathways.
Research in the Bartek lab focuses on various mechanistic aspects of the DDR and DNA repair pathways. Of particular interest is discovery of targets and markers for personalized cancer treatment and finding novel components or mechanisms of genome integrity maintenance. Another of our long-term goals is to further unravel the principles of ribosome biogenesis surveillance and to understand the dynamics and the finer details of the p53 pathway in sensing ribosome dysfunction, and how ribosomal stress crosstalk with the DNA damage response.
Examples of projects currently running in the lab include: the search for new treatments and markers for malignant brain tumors with a focus on the nucleolus and ribosome biogenesis; characterization of proteins involved in the DNA damage response in particular in R loop formation and resolution; characterization of proteins involved in rRNA processing and mRNA translation; and the exploration of novel links between the nucleolus and the protein degradation machinery.
- Andrea Björk, postdoctoral researcher, 2016-2021
- Terezie Imrachova, visiting researcher, 2021
- Athina Eleftheraki, master student, 2021
- Karla Paola Leal Villegas, visiting PhD student, 2021
- Gábor Merényi, research assistant, 2019-2021
- Sidorela Selami, research assistant, 2020
- Kenneth Schou, postdoctoral researcher, 2017-2020
- Fenne Van Dongen, master student, 2019
- Anastasios Mastroanastasiou, undergraduate summer intern, 2018
- Kaveh Moazemi-Goudarzi, PhD student, 2015-2018
- Annika Ranta, undergraduate summer intern, 2017
- Alexandros Iskantar, undergraduate student Erasmus+, 2017
The exon-junction complex helicase eIF4A3 controls cell fate via coordinated regulation of ribosome biogenesis and translational output.
Kanellis DC, Espinoza JA, Zisi A, Sakkas E, Bartkova J, Katsori AM, Boström J, Dyrskjøt L, Broholm H, Altun M, Elsässer SJ, Lindström MS, Bartek J
Sci Adv 2021 Aug;7(32):
Human RTEL1 associates with Poldip3 to facilitate responses to replication stress and R-loop resolution.
Björkman A, Johansen SL, Lin L, Schertzer M, Kanellis DC, Katsori AM, Christensen ST, Luo Y, Andersen JS, Elsässer SJ, Londono-Vallejo A, Bartek J, Schou KB
Genes Dev 2020 08;34(15-16):1065-1074
The antimalarial drug amodiaquine stabilizes p53 through ribosome biogenesis stress, independently of its autophagy-inhibitory activity.
Espinoza JA, Zisi A, Kanellis DC, Carreras-Puigvert J, Henriksson M, Hühn D, et al
Cell Death Differ. 2020 Feb;27(2):773-789
Reduced Expression of PROX1 Transitions Glioblastoma Cells into a Mesenchymal Gene Expression Subtype.
Goudarzi KM, Espinoza JA, Guo M, Bartek J, Nistér M, Lindström MS, et al
Cancer Res. 2018 10;78(20):5901-5916
Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4.
Skrott Z, Mistrik M, Andersen KK, Friis S, Majera D, Gursky J, et al
Nature 2017 12;552(7684):194-199
Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing.
Galanos P, Vougas K, Walter D, Polyzos A, Maya-Mendoza A, Haagensen EJ, et al
Nat. Cell Biol. 2016 07;18(7):777-89
TOPBP1 regulates RAD51 phosphorylation and chromatin loading and determines PARP inhibitor sensitivity.
Moudry P, Watanabe K, Wolanin KM, Bartkova J, Wassing IE, Watanabe S, et al
J. Cell Biol. 2016 Feb;212(3):281-8
A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer.
Dietlein F, Kalb B, Jokic M, Noll EM, Strong A, Tharun L, et al
Cell 2015 Jul;162(1):146-59
REV7 counteracts DNA double-strand break resection and affects PARP inhibition.
Xu G, Chapman JR, Brandsma I, Yuan J, Mistrik M, Bouwman P, et al
Nature 2015 May;521(7553):541-544
ATR mediates a checkpoint at the nuclear envelope in response to mechanical stress.
Kumar A, Mazzanti M, Mistrik M, Kosar M, Beznoussenko GV, Mironov AA, et al
Cell 2014 Jul;158(3):633-46
ATR prohibits replication catastrophe by preventing global exhaustion of RPA.
Toledo LI, Altmeyer M, Rask MB, Lukas C, Larsen DH, Povlsen LK, et al
Cell 2013 Nov;155(5):1088-103
JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks.
Watanabe S, Watanabe K, Akimov V, Bartkova J, Blagoev B, Lukas J, et al
Nat. Struct. Mol. Biol. 2013 Dec;20(12):1425-33
The DNA-damage response in human biology and disease.
Jackson SP, Bartek J
Nature 2009 Oct;461(7267):1071-8
Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints.
Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N, et al
Nature 2006 Nov;444(7119):633-7