Duxin Group – University of Copenhagen

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Duxin Group

The Duxin group (Mechanisms of DNA repair & DNA replication) at CPR was established in August 2016 and is headed by associate professor and group leader Julien P. Duxin

First row from left: Nicolai Larsen, Julien Duxin, Irene Gallina, Lisa Schubert (shared with Mailand group), Mathilde Hyldig

Research area

Our cells are under continuous assault from reactive compounds that damage their DNA. To counter the accumulation of DNA lesions, cells have evolved specialized repair pathways that are remarkably conserved throughout evolution. We are particularly interested in delineating repair pathways that are coupled to DNA replication as the process of copying the genome often triggers DNA repair.  Conversely, failure to efficiently replicate the genome undergoing genotoxic stress is linked to a variety of cancer and accelerated aging syndromes. By delineating these repair mechanisms, we aim to identify the causes underlying these genetic disorders and provide important molecular clues that will lead to better treatments in the clinic.

In our group, we use protein extracts derived from the eggs of the African clawed frog, Xenopus laevis. These protein extracts have the extraordinary capacity to reiterate in a test tube the fundamental processes of genome duplication and maintenance. The use of these extracts recently led to the discovery of a novel repair pathway that specifically removes DNA-protein crosslinks during S phase (Duxin et al., 2014, Cell). DNA-protein crosslinks, also known as DPCs, are toxic DNA lesions induced by a variety of endogeonous or exogeonous crosslinking agents and are suspected to cause cancer and aging. When a replication fork encounters a DPC, the replisome stalls due to the collision of the replicative helicase with the protein adduct (Figure 1, i).

The DPC is then proteolytically degraded into a peptide adduct (Figure 1, ii) that is amenable for replication fork bypass (Figure 1, iii). This repair process illustrates the incredible orchestration of events that must occur at the replication fork in order to specifically target toxic protein adducts to degradation while maintaining a functional replisome. In our group, we are interested in understanding how these different events are coordinated and identify the key players that participate in each of these steps so that we can understand this reaction in great detail.