Date

Tuesday 10 Nov 2026

Time

15:15 - 15:45

Location

BW031

Supervisor

Madeline Kavanagh

Jury

Rene Olsthoorn

External supervisor

Jacqueline Jacobs

DNA damage signaling is triggered by the recognition of DNA damage and is essential for coordinating the cellular response and facilitating DNA repair. Previous screening approaches identified Lin37 as a potential regulator of DNA repair and ATM signaling. Lin37 is a component of the MuvB core complex and has primarily been studied as a regulator of cell cycle dependent transcription. This study investigated the role of Lin37 in DNA damage signaling following telomere deprotection and characterized the effects of Lin37 loss on protein expression genes in cycling cells. Loss of Lin37 was associated with reduced ATM activation and KAP1 phosphorylation following telomere deprotection in both mouse and human cell models, supporting a role for Lin37 in ATM dependent DNA damage signaling. The pKAP1 signaling defect could not be attributed to altered MRN complex expression, a general dysfunction of the MuvB core complex or FOXM1 related mechanisms. Instead, the rescue of pKAP1 signaling upon Lin37 re expression supports a Lin37 specific role in regulating DNA damage signaling, although the underlying mechanism remains to be determined. Proteomic analysis further showed that Lin37 loss in cycling cells resulted in broad upregulation of cell cycle associated proteins, particularly those involved in M-phase progression. These changes occurred without a clear alteration in cell cycle distribution, indicating that they were not simply explained by differences in cell cycle composition. Together, these findings support a role for Lin37 in DNA damage signaling following telomere deprotection and show that Lin37 loss affects the expression of cell cycle associated proteins in cycling cells. Further studies are required to establish the molecular mechanism linking Lin37 to ATM–KAP1 signaling.