Universität zu Köln

Doll, Markus Alexander, Soltanmohammadi, Najmeh and Schumacher, Bjoern (2019). ALG-2/AGO-Dependent mir-35 Family Regulates DNA Damage-Induced Apoptosis Through MPK-1/ERK MAPK Signaling Downstream of the Core Apoptotic Machinery in Caenorhabditis elegans. Genetics, 213 (1). S. 173 - 195. BETHESDA: GENETICS SOCIETY AMERICA. ISSN 1943-2631

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Abstract

MicroRNAs (miRNAs) associate with argonaute (AGO) proteins to post-transcriptionally modulate the expression of genes involved in various cellular processes. Herein, we show that loss of the Caenorhabditis elegans AGO gene results in rapid and significantly increased germ cell apoptosis in response to DNA damage inflicted by ionizing radiation (IR). We demonstrate that the abnormal apoptosis phenotype in mutant animals can be explained by reduced expression of miRNA family members. We show that the increased apoptosis levels in IR-treated or family mutants depend on a transient hyperactivation of the C. elegans ERK1/2 MAPK ortholog in dying germ cells. Unexpectedly, phosphorylation occurs downstream of caspase activation and depends at least in part on a functional cell corpse-engulfment machinery. Therefore, we propose a refined mechanism, in which an initial proapoptotic stimulus by the core apoptotic machinery initiates the engulfment process, which in turn activates MAPK signaling to facilitate the demise of genomically compromised germ cells.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Doll, Markus Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Soltanmohammadi, Najmeh UNSPECIFIED UNSPECIFIED UNSPECIFIED Schumacher, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-142737
DOI:	10.1534/genetics.119.302458
Journal or Publication Title:	Genetics
Volume:	213
Number:	1
Page Range:	S. 173 - 195
Date:	2019
Publisher:	GENETICS SOCIETY AMERICA
Place of Publication:	BETHESDA
ISSN:	1943-2631
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROGRAMMED CELL-DEATH; ACTIVATED PROTEIN-KINASE; C. ELEGANS; IONIZING-RADIATION; TUMOR-SUPPRESSOR; NEGATIVE REGULATION; CORPSE ENGULFMENT; GENETIC-CONTROL; CYCLE ARREST; CANCER CELLS Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14273