Skip to main content

Helle Ulrich

Ubiquitin, SUMO & Genome Maintenance

Research in the Ulrich lab centres on the intersection between two primary hallmarks of ageing: genomic instability and loss of proteostasis. Whereas genome maintenance mechanisms preserve the genetic information of an organism by preventing or repairing DNA damage and assuring faithful duplication of the genome, protein quality control systems regulate the abundance of the cell’s major building blocks and safeguard their functionality. Members of the ubiquitin family play an important role in proteostasis as they control protein function, abundance and localisation. Thus, like defects in DNA repair pathways, deregulation of ubiquitin signalling is associated with many age-related diseases.

The Ulrich lab investigates the contributions of ubiquitin and the ubiquitin-like protein SUMO to the regulation of DNA replication, repair and genome stability, focusing on a pathway of DNA damage bypass that allows genome replication in the presence of DNA-damaging agents. This pathway helps cells resist genotoxic agents, but also has the potential to cause genome instability and must be tightly regulated. The lab uses a combination of genetic, genomic, molecular biological and biochemical approaches to elucidate how the ubiquitylation or SUMOylation of key replication factors regulates the replication of damaged DNA and how this is coordinated with the overall cellular DNA damage response. We have developed next generation sequencing methods for genome-wide mapping of DNA lesions and replication intermediates and are designing experimental tools to detect, manipulate or inhibit ubiquitylation and SUMOylation reactions within cells.

Research website

Positions held

  • 2018 - 2019: Executive Director, Institute of Molecular Biology (IMB), Mainz
  • Since 2013: Scientific Director, Institute of Molecular Biology (IMB), Mainz; Professor, Faculty of Biology, Johannes Gutenberg University (JGU), Mainz
  • 2004 - 2012: Group Leader, Cancer Research UK London Research Institute, Clare Hall Laboratories
  • 2000 - 2004: Group Leader, Max Planck Institute for Terrestrial Microbiology, Marburg
  • 1998 - 2000: Postdoc, Max Planck Institute for Biochemistry, Martinsried
  • 1997 - 1998: Postdoc, University of Heidelberg

Education

  • 2004: Habilitation, Faculty of Biology (Genetics), Philipps University Marburg
  • 1996: PhD in Chemistry, University of California, Berkeley
  • 1992: Diploma in Biology, Georg-August-University Göttingen

Selected publications by Helle Ulrich

Shi J, Hauschulte K, Mikicic I, Maharjan S, Arz V, Strauch T, Heidelberger JB, Schaefer JV, Dreier B, Plückthun A, Beli P, Ulrich HD# and Wollscheid HP# (2023) Nuclear myosin VI maintains replication fork stability. Nat Commun, 14:3787 (#indicates joint correspondence)  Link

Yakoub G, Choi YS, Wong RP, Strauch T, Ann KJ, Cohen RE and Ulrich HD (2023) Avidity-based biosensors for ubiquitylated PCNA reveal choreography of DNA damage bypass. Sci Adv, 9:eadf3041 Link

Wegmann S*, Meister C*, Renz C, Yakoub G, Wollscheid HP, Takahashi DT, Mikicic I, Beli P and Ulrich HD (2022) Linkage reprogramming by tailor-made E3s reveals polyubiquitin chain requirements in DNA-damage bypass. Mol Cell, 82:1589–1602.e5 (*indicates joint contribution) Link

Sriramachandran AM, Petrosino G, Méndez-Lago M, Schäfer AJ, Batista-Nascimento LS, Zilio N# and Ulrich HD# (2020) Genome-wide nucleotide-resolution mapping of DNA replication patterns, single-strand breaks, and lesions by GLOE-SeqMol Cell, 78:975-985.e7 (#indicates joint correspondence) Link

Wong RP, García-Rodríguez N, Zilio N, Hanulová M and Ulrich HD (2020) Processing of DNA polymerase-blocking lesions during genome replication Is spatially and temporally segregated from replication forksMol Cell, 77:3–16.e4 Link

García‐Rodríguez N, Morawska M, Wong RP, Daigaku Y and Ulrich HD (2018) Spatial separation between replisome‐ and template‐induced replication stress signalingEMBO J, 37:e98369 Link