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PhD project: Assembly and signaling functions of polyubiquitin chains in damage bypass

In the field of  “Ubiquitin Signaling in DNA damage processing during replication” the research group of Prof. Helle Ulrich offers the following PhD project: Assembly and signaling functions of polyubiquitin chains in damage bypass


The proposed project aims at understanding the mechanism and regulation of polyubiquitin-dependent template switching. Critical to this goal is to reveal the signaling properties of the K63-linked polyubiquitin chain on PCNA. Towards this end, the lab is currently performing a series of screens in budding yeast in order to identify new interaction partners of polyubiquitylated PCNA. The proposed project will build on these studies by characterizing the candidate factors isolated in these screens, examining their contributions to damage bypass genetically, integrating their activities into the overall damage response and assessing whether potential homologues fulfill related functions in vertebrate cells. In parallel, we will perform a genetic and biochemical characterization of the ubiquitin ligase (E3) Rad5 that mediates PCNA polyubiquitylation in order to reveal how it is activated in vivo, responds to different types of damage and recognizes and modifies its substrate. In addition to the catalytic RING finger that marks Rad5 as an E3 ligase, the protein and its human homologues contain DNA-binding and chromatin remodeling domains of poorly characterized function. Their contributions to ubiquitin-mediated damage bypass and potentially other pathways of genome maintenance will be examined by means of genetic analyses as well as in vitro experiments with purified recombinant proteins, addressing DNA binding, ATPase, helicase and fork remodeling activities. In this manner, we will gain insight into how the choice between mutagenic and error-free pathways of replicative damage bypass is accomplished in response to different challenges, and how it influences efficiency and fidelity of lesion processing.

We offer
• The possibility to work on a cutting-edge project using state-of-the-art technology in a highly motivated research team
• A stimulating, diverse and international research environment
• Advanced training opportunities
• A competitive stipend

Required qualifications
• Master or Diploma
• Motivation to solve complex biological problems
• Excellent communication skills

Starting date: 1 April 2016 or later
Duration of stipend: 3 years, with the possibility of extension
Deadline for registration (exclusively online via web form):  8 November 2015

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While applying for the job please refer to jobvector and use the following reference number: JV-C9-HU

About Institute of Molecular Biology gGmbH

Our International PhD Programme on the “Gene Regulation, Epigenetics and DNA Damage Response” gives talented and enthusiastic students the opportunity to undertake PhD research at the cutting edge of modern biology. Our groups cover a broad range of expertise and include leading biochemists, geneticists, cell and developmental biologists who study the molecular mechanisms of...

More about Institute of Molecular Biology gGmbH

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