Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-61840
Dittrich, Christina M; Kratz, Katja; Sendoel, Ataman; Gruenbaum, Yosef; Jiricny, Josef; Hengartner, Michael O (2012). LEM-3 - A LEM domain containing nuclease involved in the DNA damage response in C. elegans. PLoS ONE, 7(2):e24555.
The small nematode Caenorhabditis elegans displays a spectrum of DNA damage responses similar to humans. In order to identify new DNA damage response genes, we isolated in a forward genetic screen 14 new mutations conferring hypersensitivity to ionizing radiation. We present here our characterization of lem-3, one of the genes identified in this screen. LEM-3 contains a LEM domain and a GIY nuclease domain. We confirm that LEM-3 has DNase activity in vitro. lem-3(lf) mutants are hypersensitive to various types of DNA damage, including ionizing radiation, UV-C light and crosslinking agents. Embryos from irradiated lem-3 hermaphrodites displayed severe defects during cell division, including chromosome mis-segregation and anaphase bridges. The mitotic defects observed in irradiated lem-3 mutant embryos are similar to those found in baf-1 (barrier-to-autointegration factor) mutants. The baf-1 gene codes for an essential and highly conserved protein known to interact with the other two C. elegans LEM domain proteins, LEM-2 and EMR-1. We show that baf-1, lem-2, and emr-1 mutants are also hypersensitive to DNA damage and that loss of lem-3 sensitizes baf-1 mutants even in the absence of DNA damage. Our data suggest that BAF-1, together with the LEM domain proteins, plays an important role following DNA damage - possibly by promoting the reorganization of damaged chromatin.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Molecular Cancer Research|
07 Faculty of Science > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Life Sciences
|DDC:||570 Life sciences; biology|
|Date:||23 February 2012|
|Deposited On:||26 Apr 2012 08:48|
|Last Modified:||17 Dec 2012 02:13|
|Publisher:||Public Library of Science|
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