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A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Stempor, Przemyslaw  ORCID logo  https://orcid.org/0000-0002-9464-7475
Gaarenstroom, Tessa 
Wysolmerski, Brian 
Dong, Yan 

Abstract

Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set of C. elegans heterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways. Remarkably, fertility of heterochromatin mutants could be partially restored by inhibiting cep-1/p53, endogenous meiotic double strand breaks, or the expression of MIRAGE1 DNA transposons. Functional redundancy among factors and pathways underlies the importance of safeguarding the genome through multiple means.

Description

Keywords

C. elegans, DNA damage, chromosomes, evolutionary biology, genes, genomics, germ line, heterochromatin, nuclear RNAi, piRNA, repetitive elements, Animals, Apoptosis, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Chromosomal Proteins, Non-Histone, DNA Repair, Gene Expression Regulation, Germ Cells, Heterochromatin, Interspersed Repetitive Sequences, RNA Interference, RNA, Small Interfering

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

6

Publisher

eLife Sciences Publications, Ltd
Sponsorship
Canadian Institutes of Health Research (129816)
Wellcome Trust (101863/Z/13/Z)
Wellcome Trust (104640/Z/14/Z)
Cancer Research UK (18583)
Wellcome Trust (092096/Z/10/Z)
Wellcome Trust (054523/Z/98/C)
Cancer Research Uk (None)
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