Individual
DC projects

Research project

Modulation of NAD+ -dependent PARP1/2 activity on chromatin by regulatory cofactors and impact on cancer

Rationale and objectives:

Cancer treatments inhibiting NAD+ dependent PARPs are limited by toxicity. Targeting co-factors has the potential to inhibit cancer-specific PARP1 activities without affecting essential PARP function in healthy cells.

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We plan:
• To study how distinct PARP cofactors impact the NAD+
-dependent poly-ADP-ribosylation activity of PARP1 and PARP2.
• To dissect the role of these cofactors in the PARP1/2-dependent recruitment of PAR-dependent factors to DNA damage sites.
• To measure how PARP1/2-activity modulating cofactors impact the sensitivity of cancer cells to PARP inhibitors.

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Envisioned Secondments

IJC (Buschbeck) months 20-24 (5 months) to learn how to analyze early drug responses with SLAM-seq

Recruitment

The estimated annual gross salary for the fellow will be €38.000 without family allowance; €45.000 with family allowance (approx.).