At IMB, we explore the molecular biology of the nucleus with an overarching focus on gene regulation, epigenetics & genome stability

Ubiquitin, SUMO and Genome Maintenance

Helle Ulrich

Research in my lab centres on the contributions of two posttranslational protein modifiers, ubiquitin and SUMO, to the regulation of various cellular processes. We are particularly interested in 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. In addition, we investigate the relevance of polyubiquitin chains and their geometries to ubiquitin signalling in other contexts.

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 damage bypass is coordinated with the overall cellular DNA damage response. We have developed next generation sequencing methods for the genome-wide mapping of DNA lesions and replication intermediates. In addition, we are designing experimental tools to detect, manipulate or inhibit ubiquitylation or sumoylation reactions within yeast and mammalian 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

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-Seq. Mol 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 forks. Mol Cell, 77:3–16.e4 Link

Sriramachandran AM, Meyer-Teschendorf K, Pabst S, Ulrich HD, Gehring NH, Hofmann K, Praefcke GJK and Dohmen RJ (2019) Arkadia/RNF111 is a SUMO-targeted ubiquitin ligase with preference for substrates marked with SUMO1-capped SUMO2/3 chain. Nat Commun, 10:3678 Link

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

Hung SH, Wong RP, Ulrich HD# and Kao CF# (2017) Monoubiquitylation of histone H2B contributes to the bypass of DNA damage during and after DNA replication. Proc Natl Acad Sci USA, 114:E2205–E2214 (#indicates joint correspondence) Link