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Cell Cycle Analysis in the C. elegans Germline with the Thymidine Analog EdU
Published on: October 22, 2018
NER and HR pathways act sequentially to promote UV-C-induced germ cell apoptosis in Caenorhabditis elegans
L Stergiou1, R Eberhard, K Doukoumetzidis
1Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, Zurich, Switzerland.
Abstract:
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.
Insights
Ultraviolet (UV) radiation triggers DNA damage responses. DNA repair pathways, nucleotide excision repair (NER) and homologous recombination (HR), cooperate to signal for apoptosis in germ cells.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Ultraviolet (UV) radiation causes DNA damage, initiating cellular responses like DNA repair, cell cycle arrest, and apoptosis.
- Understanding the precise molecular pathways involved in UV-induced apoptosis is crucial for comprehending cell fate determination.
Purpose of the Study:
- To characterize the molecular pathway mediating UV-C-induced apoptosis in Caenorhabditis elegans meiotic germ cells.
- To elucidate the roles of DNA repair pathways in signaling UV-induced apoptosis.
Main Methods:
- Utilized the nematode Caenorhabditis elegans as a model organism.
- Investigated the involvement of nucleotide excision repair (NER) and homologous recombination (HR) pathways in UV-C-induced apoptosis.
- Examined the recruitment of the 9-1-1 complex and activation of checkpoint kinases.
Main Results:
- UV-C-induced DNA lesions require processing by the NER pathway to become pro-apoptotic.
- NER pathway activity generates DNA damage recognized by the HR pathway.
- HR pathway activity is essential for recruiting the 9-1-1 complex and activating checkpoint kinases, leading to apoptosis.
- Inhibition of either NER or HR abrogates apoptosis signaling.
Conclusions:
- Multiple DNA repair pathways, specifically NER and HR, cooperate to signal UV-induced apoptosis in germ cells.
- This coordinated DNA repair and signaling mechanism eliminates potentially hazardous cells following UV exposure.
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