Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-47983
Stergiou, L; Eberhard, R; Doukoumetzidis, K; Hengartner, M O (2011). NER and HR pathways act sequentially to promote UV-C-induced germ cell apoptosis in caenorhabditis elegans. Cell Death and Differentiation, 18(5):897-906.
|Published Version (English)|
PDF - Registered users only
|Accepted Version (English)|
Ultraviolet (UV) radiation-induced DNA damage evokes a complex network of molecular responses, which culminate in DNA repair, cell cycle arrest and apoptosis. Here, we provide an in-depth characterization of the molecular pathway that mediates UV-C-induced apoptosis of meiotic germ cells in the nematode Caenorhabditis elegans. We show that UV-C-induced DNA lesions are not directly pro-apoptotic. Rather, they must first be recognized and processed by the nucleotide excision repair (NER) pathway. Our data suggest that NER pathway activity transforms some of these lesions into other types of DNA damage, which in turn are recognized and acted upon by the homologous recombination (HR) pathway. HR pathway activity is in turn required for the recruitment of the C. elegans homolog of the yeast Rad9-Hus1-Rad1 (9-1-1) complex and activation of downstream checkpoint kinases. Blocking either the NER or HR pathway abrogates checkpoint pathway activation and UV-C-induced apoptosis. Our results show that, following UV-C, multiple DNA repair pathways can cooperate to signal to the apoptotic machinery to eliminate potentially hazardous cells.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||07 Faculty of Science > Institute of Molecular Life Sciences|
|DDC:||570 Life sciences; biology|
|Deposited On:||03 May 2011 14:10|
|Last Modified:||27 Nov 2013 22:48|
|Publisher:||Nature Publishing Group|
|Citations:||Web of Science®. Times Cited: 12|
Scopus®. Citation Count: 13
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page