Genome Stability · Ubiquitin Signalling

Genome Stability Lab (GSL)

The University of Manchester

Welcome to our lab

Christine M. Schmidt — Genome Stability Lab

We study how ubiquitin and ubiquitin‑like signalling shapes DNA repair and cell‑cycle control using mechanistic biochemistry and quantitative imaging.

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Principal investigator

Professor Christine M. Schmidt

Senior Lecturer, Division of Cancer Sciences

Christine Schmidt leads the Genome Stability Lab at The University of Manchester. Her work probes the role of ubiquitin and ubiquitin‑like modifiers in DNA repair and cancer‑relevant genome instability.

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Research programmes

What we study

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Figure from 'Site‑selective photo‑crosslinking for the characterisation of transient ubiquitin‑like protein‑protein interactions' (PLoS ONE, 2025). Example photo‑crosslinking data and mapped interaction sites illustrating capture of transient, non‑covalent contacts between ubiquitin‑like modifiers and receptor domains — relevant to mapping weak recruitment events at DNA double‑strand breaks.

How do ubiquitin‑like receptors and transient interactions coordinate DNA repair?

Transient, non‑covalent interactions between ubiquitin‑like proteins and their receptors define recruitment and activity of repair complexes. We aim to map these weak contacts and understand their functional consequences for double‑strand break repair.

Figure 2 from the Nucleic Acids Research (2022) open‑access article describing SUMO‑binding modules and their linkage to NHEJ factor engagement on chromatin (relevant to chromatin engagement of NHEJ machinery).

What controls chromatin engagement of non‑homologous end‑joining machinery?

Chromatin context and post‑translational modifications control assembly of non‑homologous end‑joining (NHEJ) complexes. We examine how UBL signalling and chromatin modifiers regulate NHEJ factor engagement at double‑strand breaks.

Figure illustrating structure and functional roles of UBE2D-family E2 enzymes and schematic models of E2–E3–substrate relationships relevant to DSB repair (useful as an open‑access depiction of E2 enzyme mechanisms and context for interrogating which E2s bias repair‑pathway choice). Source: 'The UBE2D ubiquitin conjugating enzymes: Potential regulatory hubs in development, disease and evolution' (PMC9790923).

Which E2 enzymes set the stage for repair‑pathway decisions?

E2 ubiquitin‑conjugating enzymes direct ubiquitylation events that bias repair toward end‑joining or homologous recombination. We dissect E2–E3 axes and their downstream substrates to understand how conjugation specificity impacts repair outcomes.

Review figure summarising ubiquitin/UBL proteases in DNA repair (open access review figure; see PMC article).

How do deubiquitylating and UBL‑processing proteases sculpt repair complexes?

Removal and editing of ubiquitin and UBL signals by dedicated proteases is essential to regulate the lifetime and activity of repair complexes. This programme focuses on proofreading and reversal mechanisms that shape repair dynamics.

Selected publications

Recent and defining work

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2025

Site‑selective photo‑crosslinking for the characterisation of transient ubiquitin‑like protein‑protein interactions

PLoS ONE

↗2025

UFMylation orchestrates chromatin engagement of core NHEJ components to promote DNA double‑strand break repair

bioRxiv (preprint)

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2024

DoUBLing up: ubiquitin and ubiquitin‑like proteases in genome stability

Biochemical Journal

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2024

Small‑molecule inhibition of CBX4/7 hypersensitises homologous recombination‑impaired cancer to radiation

Cancers

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2022

Microarray screening reveals two non‑conventional SUMO‑binding modules linked to DNA repair by non‑homologous end‑joining

Nucleic Acids Research

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Students and collaborators welcome

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