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Transcription-Replication Conflicts under different temperatures
Helmholtz Munich | Anna Dumitriu

Chromosome Dynamics and Genome Stability

Hamperl Lab

About our Research

We study how DNA replication and transcription can occur simultaneously without major accidents that cause DNA damage and genome instability.

Our genetic information stored in DNA must be accurately expressed, replicated, and maintained to allow cellular proliferation, differentiation, and development in a multicellular organism. How all these processes are coordinated so that they can progress simultaneously on the DNA, free from errors, is poorly understood. Yet the knowledge of the molecular players is essential to uncover how DNA damage and genome instability emerge during the progression of dreadful diseases, such as cancer.

DNA replication and transcription complexes initiate the synthesis of complementary DNA or RNA strands from distinct genomic locations, termed origins and promoters, respectively. Importantly, chromatin presents the natural substrate of these DNA-templated processes. Eukaryotic chromatin is associated, interpreted, and modified by numerous constituents, including DNA and RNA metabolizing machineries, transcription factors, chromatin-modifying proteins, and more. To understand the molecular basis of these DNA transactions, it is critical to define the collective changes of the chromatin structure at the genomic regions where the transcription and replication machineries assemble and drive their biological reactions.

We aim to identify the molecular players and the sequence of events that allow replication and transcription initiation. Our studies will expand our knowledge about how replication timing and gene expression are coordinated in eukaryotic cells and deregulated in a myriad of human disease states.

Once initiated, transcription and replication machineries translocate along the same DNA template, often in opposing directions and at different rates. Mounting evidence suggests that transcription complexes can encounter replication forks on eukaryotic chromosomes. Cells rely on numerous mechanisms to tolerate and resolve such transcription-replication conflicts. The absence of these mechanisms can lead to catastrophic effects on genome stability and cell viability.

We recently established an in vivo system to reconstitute and analyze encounters between the replication fork and a specific type of transcriptional barrier named R-loop in an inducible and localized fashion. Using this system and other cell biological, genetic and proteomic approaches, we aim to elucidate the genetic and epigenetic mechanisms how cells respond, tolerate and resolve different types of transcription-replication conflicts. Our studies will provide insights into how transcription-replication conflicts causes genome instability, often seen during development, in cancer, and many other physiological and disease contexts.

 

Eukaryotic DNA replication starts at multiple sites throughout the genome and is necessarily coordinated with other chromosomal processes including transcription, chromatin assembly and maturation, recombination and DNA repair. Notably, chromosomes provide the fundamental scaffold for all these dynamic and in part simultaneously occurring processes. Our ultimate goal is to understand the genetic and epigenetic principles of how these fundamental processes are regulated and coordinated to work together on the genome of eukaryotic cells.

We use innovative cell biological, genetic and proteomic approaches in yeast and human cells. We are particularly interested to identify the molecular players and characterize the sequence of events that allow DNA replication and transcription to occur simultaneously on our chromosomes - without major accidents leading to DNA damage and genome instability, a hallmark of cancer and many other human diseases.

DNA replication and transcription complexes initiate the synthesis of complementary DNA or RNA strands from distinct genomic locations, termed origins and promoters, respectively. Importantly, chromatin presents the natural substrate of these DNA-templated processes. Eukaryotic chromatin is associated, interpreted, and modified by numerous constituents, including DNA and RNA metabolizing machineries, transcription factors, chromatin-modifying proteins, and more. To understand the molecular basis of these DNA transactions, it is critical to define the collective changes of the chromatin structure at the genomic regions where the transcription and replication machineries assemble and drive their biological reactions.

We aim to identify the molecular players and the sequence of events that allow replication and transcription initiation. Our studies will expand our knowledge about how replication timing and gene expression are coordinated in eukaryotic cells and deregulated in a myriad of human disease states.

Once initiated, transcription and replication machineries translocate along the same DNA template, often in opposing directions and at different rates. Mounting evidence suggests that transcription complexes can encounter replication forks on eukaryotic chromosomes. Cells rely on numerous mechanisms to tolerate and resolve such transcription-replication conflicts. The absence of these mechanisms can lead to catastrophic effects on genome stability and cell viability.

We recently established an in vivo system to reconstitute and analyze encounters between the replication fork and a specific type of transcriptional barrier named R-loop in an inducible and localized fashion. Using this system and other cell biological, genetic and proteomic approaches, we aim to elucidate the genetic and epigenetic mechanisms how cells respond, tolerate and resolve different types of transcription-replication conflicts. Our studies will provide insights into how transcription-replication conflicts causes genome instability, often seen during development, in cancer, and many other physiological and disease contexts.

 

Eukaryotic DNA replication starts at multiple sites throughout the genome and is necessarily coordinated with other chromosomal processes including transcription, chromatin assembly and maturation, recombination and DNA repair. Notably, chromosomes provide the fundamental scaffold for all these dynamic and in part simultaneously occurring processes. Our ultimate goal is to understand the genetic and epigenetic principles of how these fundamental processes are regulated and coordinated to work together on the genome of eukaryotic cells.

We use innovative cell biological, genetic and proteomic approaches in yeast and human cells. We are particularly interested to identify the molecular players and characterize the sequence of events that allow DNA replication and transcription to occur simultaneously on our chromosomes - without major accidents leading to DNA damage and genome instability, a hallmark of cancer and many other human diseases.

The Hamperl Lab

Dr. Stephan Hamperl

Group Leader

Stephan did his undergraduate studies at the University of Regensburg where he also performed his PhD research with Dr Joachim Griesenbeck. He then moved to Stanford University in California to conduct his postdoctoral research in Karlene Cimprich’s lab before returning to Germany to establish his own group at the Institute of Epigenetics and Stem Cells in March 2018.

Nationality: German
 

Portrait Marcel Werner

Marcel Werner

Doctoral Researcher

Marcel obtained his bachelor’s degree in Molecular Medicine at the University of Goettingen, where he also performed his master’s degree in the International Max Planck Research School for Molecular Biology. For his master’s thesis, he joined the lab of Patrick Cramer, studying the effect of cyclin-dependent kinase 7 (CDK7) inhibition on transcription regulation in human cells. Marcel joined the lab as a PhD student in December 2020.

Research interests: Transcription-replication conflict-driven chromatin changes and genomic instability

Nationality: German

Manuel Trauner

Doctoral Researcher

Manuel pursued his undergraduate degree at the University of Bayreuth, followed by a master's at LMU Munich. He engaged with 3D cell printing in Munich's 2016 iGEM team and did his master's thesis in the group of Dr. Jürg Müller at the Max-Planck Institute for Biochemistry. He was involved in bioinformatic projects in the group of Prof. João Pedro de Magalhães in Liverpool, UK. Supervised by Dr. Eva Hörmanseder, Manuel investigated H3K4me3 propagation in early Xenopus embryogenesis in the group of Sir John Gurdon at the University of Cambridge, UK. He also gained business insights working as a Venture Fellow Assistant at Apollo Health Ventures, responsible for scientific due diligence. Currently, Manuel is developing software tools for automated image and data analysis in the lab. Furthermore, he is exploring novel in vitro systems to study transcription-replication conflicts in a mammalian cell line.

Dr. Maxime Lalonde

Postdoc

Maxime performed his PhD studying the telomerase RNA and long non-coding telomeric RNAs dynamics and recruitment at telomeres in S.cerevisiae in Montreal University in Quebec, Canada under Dr. Pascal Chartrand supervision. He is now doing his postdoctoral studies at the Institute of Epigenetics and Stem Cells in Dr. Stephan Hamperl lab since November 2020 where he is interested in the interplay between transcription-replication coordination and cell fate maintenance in mouse embryonic stem cells.

Nationality: Canadian

Atiqa Sajid photo

Atiqa Sajid

Doctoral Researcher

Atiqa obtained her Bachelor’s degree in Biotechnology from the University of Karachi and a Master’s in Biosciences from Shaheed Zulfikar Ali Bhutto Institute of Science and Technology, Karachi, Pakistan. After her Masters, she joined the Aga Khan University, Center for Regenerative Medicine and Stem Cell Research as a research associate where she focused on understanding the 3D genome organization of human prophase nuclei. Atiqa joined Hamperl lab as a doctoral student in December 2022 to work on the single-molecule analysis of replication origin chromatin.

Clare_ShukKwan.png

Dr. Clare Shuk Kwan Lee

Postdoc

Clare did her undergraduate and master studies at the Hong Kong University of Science and Technology (HKUST). She then performed her PhD research with Dr King-Ho Cheung at the University of Hong Kong. She then returned to HKUST to conduct her postdoctoral research in Bik Tye’s DNA replication lab before going to Germany to continue her postdoctoral research in Stephan Hamperl’s lab at the Institute of Epigenetics and Stem Cells in June 2022.

Nationality: Hong Kong SAR

Ioannis Tsirkas Portrait

Dr. Ioannis Tsirkas

Postdoc

 

...for I was conscious that I knew practically nothing...

...what I do not know, I do not think I know either...

                               Plato, Apology

Augusto Chaves Murriello

Augusto Chaves Muriello

Lab Manager

Augusto studied for a “Licenciatura en Biologia” at the University of Buenos Aires. He worked on his thesis at the institute of biosciences, biotechnology, and translational biology where he studied the role of genetic mutations in combined pituitary hormone deficiency under Dr. Maria Ines Perez Millan. He then moved to Germany to work at the Hamperl Lab as a lab manager.

Nationality: Argentina

Elizabeth Marquez Gomez

Research Assistant – Bioinformatics

Elizabeth graduated with honors in Genomic Sciences from the National Autonomous University of Mexico (UNAM) in 2023. Driven by her interest in human disease, she joined Vijay's lab at La Jolla Institute for Immunology in California in 2021. There, she contributed to the research focused on the identification and characterization of the role of causal genetic variants in human disease on a genome-wide level. In February 2024, she transitioned to Hamperl's lab at the Institute of Epigenetics and Stem Cells, furthering her scientific journey.

Research interests: human diseases, developmental epigenetics, evolution, and computational biology.

Nationality: Mexican

Recent Publications

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Contact

Laura Grodtmann porttrait

Laura Grodtmann

Administrative Assistant

Building 90, Room 105