Loss of ubiquitin E2 Ube2w rescues hypersensitivity of Rnf4 mutant cells to DNA damage

SUMO and ubiquitin play important roles in the response of cells to DNA damage. These pathways are linked by the SUMO Targeted ubiquitin Ligase Rnf4 that catalyses transfer of ubiquitin from a ubiquitin loaded E2 conjugating enzyme to a polySUMO modified substrate. Rnf4 can functionally interact with multiple E2s, including Ube2w, in vitro. Chicken cells lacking Rnf4 are hypersensitive to hyroxyurea, DNA alkylating drugs and DNA crosslinking agents, but this sensitivity is suppressed by simultaneous depletion of Ube2w. Cells depleted of Ube2w alone are not hypersensitive to the same DNA damaging agents. Similar results were also obtained in human cells. These data indicate that Ube2w does not have an essential role in the DNA damage response, but is deleterious in the absence of Rnf4. Thus, although Rnf4 and Ube2w functionally interact in vitro, our genetic experiments indicate that in response to DNA damage Ube2w and Rnf4 function in distinct pathways

Bolaang Mongondowsch-Nederlandsch woordenboek, met Nederlandsch-Bolaang Mongondowsch register

xii, 635 p.; 231/2 cm

Endolymphatic hydrops after total dissection or cauterization of the distal portion of the endolymphatic sac

In this study, a more subtle animal model of Meniere's disease is investigated by damaging the distal portion of the endolymphatic sac by dissection or cauterization to produce mild dysfunction of endolymphatic outflow. Cauterization resulted in low degrees of hydrops without any correlation with the inflicted damage. Total dissection of the distal portion of the sac adjacent to the sigmoid sinus produced moderate to severe endolymphatic hydrops with interanimal variation. The consequences of these relatively severe effects, in relation to the mild damage of the endolymphatic sac, and the influence on damaged and undamaged parts of the endolymphatic sac will be discussed