Jana Dobrovolná
Jana Dobrovolná, Ph.D.
Jana Dobrovolná, Ph.D.
Address:  Institute of Molecular Genetics
of the Czech Academy of Sciences
Vídeňská 1083
142 20 Prague 4, Czech Republic
Phone:
Phone (laboratory):
+420 241 063 127
+420 241 063 112
Fax:+420 241 062 289
E-mail:jana.dobrovolna@img.cas.cz

Biography

Education

2002 - 2008 Ph.D. studies at the Faculty of Science, Charles University in Prague, Czech Republic
Thesis: Regulation of promyelocytic leukemia (PML) gene expression.
Supervisor: Zdenek Hodny, MD, PhD and Prof. Pavel Hozak, PhD
1995 - 2001 Master’s degree in Biology at Charles University in Prague, Faculty of Natural Sciences, Czech Republic
Thesis: The study of hormone induced changes in G-protein content in membrane microdomains
Supervisor: Doc. Petr Svoboda, PhD

Research Experience

01/2020 – presentResearch fellow at the Laboratory of Cancer Cell Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Czech Republic.
Head of Department: Libor Macůrek, PhD
Head of the project: Pavel Janščák, PhD
02/2013 – presentDeputy head of Dr. Pavel Janščák
02/2013 – 12/2019Research fellow at the Department of Genome Integrity, Institute of Molecular Genetics of the Czech Academy of Sciences, Czech Republic.
Head of Department: Prof. Jiří Bártek, MD, DSc
Head of the project: Pavel Janščák, PhD
06/2008 – 12/2011Postdoctoral research fellow position at Hospital for Special Surgery, New York, N.Y., USA.
Head of Laboratory: Inez Rogatsky, PhD
07/2002 – 12/2007Research investigator at the Institute of Experimental Medicine of the Czech Academy of Sciences and the Institute of Molecular Genetics of the Czech Academy of Sciences, Department of Biology of the Cell Nucleus, Czech Republic.
Head of Department: Prof. Pavel Hozak, PhD
1996– 2001Young investigator at the Institute of Physiology of the Czech Academy of Sciences, Czech Republic.
Head of Department: Doc. Petr Svoboda, PhD

Publications

  • Isik E, Shukla K, Pospisilova M, König C, Andrs M, Rao S, Rosano V, Dobrovolna J, Krejci L, Janscak P. MutSβ-MutLβ-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops. Sci Adv. 2024 Feb 9;10(6):eadk2685
  • Andrs M, Stoy H, Boleslavska B, Chappidi N, Kanagaraj R, Nascakova Z, Menon S, Rao S, Oravetzova A, Dobrovolna J, Surendranath K, Lopes M, Janscak P. Excessive reactive oxygen species induce transcription-dependent replication stress. Nat Commun. 2023 Mar 30;14(1):1791
  • Martinikova AS, Stoyanov M, Oravetzova A, Kok YP, Yu S, Dobrovolna J, Janscak P, van Vugt M, Macurek L. PPM1D activity promotes the replication stress caused by cyclin E1 overexpression. Mol Oncol. 2023 Apr 17
  • Boleslavska B, Oravetzova A, Shukla K, Nascakova Z, Ibini ON, Hasanova Z, Andrs M, Kanagaraj R, Dobrovolna J*, Janscak P*. DDX17 helicase promotes resolution of R-loop-mediated transcription-replication conflicts in human cells. Nucleic Acids Res. 2022 Nov 28;50(21):12274-12290
  • Nascakova Z, Boleslavska B, Urban V, Oravetzova A, Vlachova E, Janscak P*, Dobrovolna J*. RAD51 Inhibition Induces R-Loop Formation in Early G1 Phase of the Cell Cycle. Int J Mol Sci. 2021 Apr 3;22(7):3740
  • Bauer M, Nascakova Z, Mihai AI, Cheng PF, Levesque MP, Lampart S, Hurwitz R, Pfannkuch L, Dobrovolna J, Jacobs M, Bartfeld S, Dohlman A, Shen X, Gall AA, Salama NR, Töpfer A, Weber A, Meyer TF, Janscak P, Müller A. The ALPK1/TIFA/NF-κB axis links a bacterial carcinogen to R-loop-induced replication stress. Nat Commun. 2020 Oct 9;11(1):5117
  • Chappidi N, Nascakova Z, Boleslavska B, Zellweger R, Isik E, Andrs M, Menon S, Dobrovolna J, Balbo Pogliano C, Matos J, Porro A, Lopes M, Janscak P.: Fork Cleavage-Religation Cycle and Active Transcription Mediate Replication Restart after Fork Stalling at Co-transcriptional R-Loops. Mol Cell 2020, 77(3):528-54
  • Andrs M, Hasanova Z, Oravetzova A, Dobrovolna J, Janscak P.: RECQ5: A Mysterious Helicase at the Interface of DNA Replication and Transcription. Genes (Basel) 2020, 11(2)
  • Teloni F, Michelena J, Lezaja A, Kilic S, Ambrosi C, Menon S, Dobrovolna J, Imhof R, Janscak P, Baubec T, Altmeyer M.: Efficient Pre-mRNA Cleavage Prevents Replication-Stress-Associated Genome Instability. Mol Cell 2019, 73(4), 670-683
  • Urban V, Dobrovolna J, Janscak P: Distinct functions of human RecQ helicases during DNA replication. Biophys Chem 2017; 225:20-26
  • Urban V, Dobrovolna J, Hühn D, Fryzelkova J, Bartek J, Janscak P: RECQ5 helicase promotes resolution of conflicts between replication and transcription in human cells. J Cell Biol 2016; 214(4):401-15
  • Chinenov Y, Gupte R, Dobrovolna J, Flammer JR, Liu B, Michelassi FE, Rogatsky I: Role of transcriptional coregulator GRIP1 in the anti-inflammatory actions of glucocorticoids. Proc Natl Acad Sci U S A 2012; 109(29):11776-81
  • Dobrovolna J, Chinenov Y, Kennedy MA, Liu B, Rogatsky I: Glucocorticoid-dependent phosphorylation of the transcriptional coregulator GRIP1. Mol Cell Biol 2012; 32(4):730-9
  • Flammer JR, Dobrovolna J, Kennedy MA, Chinenov Y, Glass CK, Ivashkiv LB, Rogatsky I: The type I interferon signaling pathway is a target for glucocorticoid inhibition. Mol Cell Biol 2010; 30(19):4564-74
  • Hubackova S, Novakova Z, Krejcikova K, Kosar M, Dobrovolna J, Duskova P, Hanzlikova H, Vancurova M, Barath P, Bartek J and Hodny Z: Regulation of the PML tumor suppressor in drug-induced senescence of human normal and cancer cells by JAK/STAT-mediated signaling. Cell Cycle 2010; 15(9):3085-99
  • Novakova Z, Hubackova S, Kosar M, Janderova-Rossmeislova L, Dobrovolna J, Vasicova P, Vancurova M, Horejsi Z, Hozak P, Bartek J and Hodny Z: Cytokine expression and signaling in drug-induced cellular senescence. Oncogene 2010; 29(2):273-84
  • Vlasakova J, Novakova Z, Rossmeislova L, Kahle M, Hozak P, Hodny Z.: Histone deacetylase inhibitors suppress IFNalpha-induced up-regulation of promyelocytic leukemia protein. Blood 2007; 109(4):1373-80
  • Janderova-Rossmeislova L, Novakova Z, Vlasakova J, Philimonenko V, Hozak P, Hodny Z.: PML protein association with specific nucleolar structures differs in normal, tumor and senescent human cells. J Struct Biol. 2007 Jul; 159(1):56-70

 

*corresponding authors

Research Interest

Role of R-loops in onset of genomic instability and counteracting molecular mechanisms

Cancer is one of the main causes of death; world-wide it accounts for 13 % of the total number of deaths. The vast majority of human cancers are linked to genome instability, a hallmark of the transition of a normal cell to a pre-cancerous cell. The pre-cancerous cells are still benign, but because of an acquired selective advantage they have an increased potential to be transformed to fully malignant cells. Activated oncogenes that can drive such a transformation were recently shown to induce extensive replication stress, e.g. stalling or collapse of replication forks, preferentially at specific genomic regions called common fragile sites (CFSs). Replication stress can result from collisions between replication machinery and oncoming transcription complexes, which can lead to the formation of highly genotoxic RNA:DNA hybrids referred to as R-loops. A link between the breakage of CFSs and the formation of R-loops as a consequence of replication/transcription encounters has recently been established. R-loops are composed of the nascent RNA annealed to the DNA template strand and unpaired complementary DNA strand that is vulnerable to breakage. Despite of growing evidence that unscheduled formation and stabilization of R-loops in eukaryotic cells challenges genomic integrity, the mechanisms involved in the resolution of these structures remain poorly understood.

The goal of our work is to advance understanding of the molecular mechanisms underlying R-loop formation, prevention and resolution and to explore the possible role of these structures in oncogene-induced DNA damage. Specifically, we aim to identify proteins that bind to R-loop structures under conditions of replication stress and to establish the functional significance of these proteins in the resolution of transcription/replication collisions and in suppression of transcription-associated genomic instability. Further, we aim to identify on genome-wide scale the loci that are prone to R-loop formation upon oncogene-induced replication stress.

 

Figure 1: Study of role of R-loops in onset of genomic instability

People

Current people in the research team
Aditya Aithal – Ph.D. student (supervisor: Pavel Janščák, co-mentor: Jana Dobrovolná)
Anna Oravetzová Huňová – Ph.D. student (supervisor: Jana Dobrovolná, co-mentor: Pavel Janščák)
Tias Saha - postdoctoral fellow (supervisor: Jana Dobrovolná, co-mentor: Pavel Janščák)
Kaustubh Shukla – postdoctoral fellow (supervisor: Pavel Janščák, co-mentor: Jana Dobrovolná)
Anton Zuev – Ph.D. student (supervisor: Jana Dobrovolná, co-mentor: Pavel Janščák)


Graduated Ph.D. students
Barbora Boleslavská (supervisor: Jana Dobrovolná, co-mentor: Pavel Janščák), graduation 2023
Zuzana Naščáková (supervisor: Jana Dobrovolná, co-mentor: Pavel Janščák), granduation 2021


Graduated M.Sc. student
Jana Fryzelková (supervisor: Jana Dobrovolná, co-mentor: Václav Urban), graduation 2017


Other past members
Martin Andrš (postdoc)
Kamila Burdová (Ph.D. student)
Zdenka Hašanová (postdoc)
Edita Křížová Vlachová (Ph.D. student)
Roman Straňanek (Ph.D. Student)
Václav Urban (Ph.D. Student)

Open Positions

Positions for undergraduate students (to achieve B.Sc. or M.Sc.) and for Ph.D. students are available.
Feel free to contact Jana Dobrovolna jana.dobrovolna@img.cas.cz for detail information any time.

Funding

  • 2021-2025, The Czech Science Foundation, EXPRO (co-PI)
  • 2020-2022, The Ministry of Education, Youth and Sports: InterAction (a principal investigator)
  • 2018-2020, The Ministry of Education, Youth and Sports: Modernization and support of research activities of the national infrastructure for biological and medical imaging Czech-BioImaging (a principal investigator of one of ten projects from the institute)
  • 2016-2017, Neuron Fund for Support of Science - Neuron Impulse 2015 (a principal investigator)
  • 2014-2016, The Ministry of Education, Youth and Sports: KONKAT II (a principal investigator)
  • 2014-2015, Czech Academy o Sciences: Postdoctoral fellowship (a principal investigator)

Collaborating Laboratories

Masaryk University
Lumír Krejčí
Kamenice 753/5
625 00 Brno
Czech Republic


University of Zurich
Pavel Janščák
Institute of Molecular Cancer Research
Winterthurerstrasse 190
CH-8057 Zurich
Switzerland

Various

Popularization of science

  • Interview for broadcasting radio station Zet (Jana Dobrovolná) 27.7.2015 (in Czech) - www.zet.cz
  • Interview for daily press iDNES (Jana Dobrovolná) 28.11.2015 (in Czech) - http://technet.idnes.cz
  • Interview for daily press Hospodářské noviny (Jana Dobrovolná) 2.12.2015 (in Czech) - http://domaci.ihned.cz

 

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