Modulation of SUMO1-TOP1 DNA damage repair by TOPORS following ovalbumin-induced oxidative stress in macrophages

Allergens, a common trigger of asthma, can lead to increased levels of reactive oxygen species (ROS) and subsequent DNA damage. However, the repair mechanism of DNA damage caused by oxidative stress in allergen-induced asthma is less known. We explored the mechanism by which topoisomerase 1 binding arginine/serine rich protein (TOPORS) regulates small ubiquitin-related modifier 1 (SUMO1) modification of TOP1 to repair DNA damage induced by ovalbumin (OVA). We tested the expression level of TOP1 in asthmatic and healthy children. OVA-induced mouse asthma model was used for further validation. The level of SUMO1-TOP1 in macrophages was studied by immunoprecipitation. The expression of TOP1 was increased in asthmatic children. The expression of TOP1 and γ Histone 2AX (γH2AX) were increased in the lung tissue of asthmatic mice. In OVA-induced macrophages, the levels of TOP1 and γH2AX were increased, while knockdown expression of TOP1 could reduce the level of γH2AX. The level of SUMO1-TOP1 in OVA-induced macrophages was increased. Interestingly, knockdown expression of TOPORS could reduce the levels of SUMO1-TOP1 in OVA-induced macrophages, while the levels of TOP1 and γH2AX were increased. Our results indicate that TOPORS regulates SUMO1 modification of TOP1 and plays an important role in the repair of DNA damage induced by OVA. DNA repair in asthma exacerbation could be a therapeutic target.