RRC ID 51451
Author Herbette M, Mercier MG, Michal F, Cluet D, Burny C, Yvert G, Robert VJ, Palladino F.
Title The C. elegans SET-2/SET1 histone H3 Lys4 (H3K4) methyltransferase preserves genome stability in the germline.
Journal DNA Repair (Amst)
Abstract Maintaining the integrity of genetic information across generations is essential for both cell survival and reproduction, and requires the timely repair of DNA damage. Histone-modifying enzymes play a central role in the DNA repair process through the deposition and removal of post-translational modifications on the histone tails. Specific histone modification act in the DNA repair process through the recruitment of proteins and complexes with specific enzymatic activities, or by altering the chromatin state at the site of DNA lesions. The conserved SET1/MLL family of histone methyltransferases (HMT) catalyzes methylation of histone H3 on Lysine 4 (H3K4), a histone modification universally associated with actively transcribed genes. Studies have focused on the role of SET1/MLL proteins in epigenetic regulation of gene expression. Much less is known on their role in the DNA repair process in a developmental context. Here we show that SET-2, the Caenorhabditis elegans orthologue of SET1, is required to preserve germline genome integrity over subsequent generations. Animals lacking the SET-2 catalytic subunit show a transgenerational increase in sensitivity to DNA damage-inducing agents that is accompanied by a defect in double-strand break (DSB) repair and chromosome fragmentation. These defects are not due to a failure to activate the DNA damage response (DDR) that allows detection, signaling and repair of DNA lesions, because cell cycle arrest and apoptosis, key components of this pathway, are efficiently induced in set-2 mutant animal. Rather, our results suggest that SET-2 plays a role in the transgenerational maintenance of genome stability by acting in DNA repair downstream of DDR signaling.
Volume 57
Pages 139-150
Published 2017-9-1
DOI 10.1016/j.dnarep.2017.07.007
PII S1568-7864(17)30270-7
PMID 28779964
MeSH Animals Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / metabolism* DNA / metabolism DNA Breaks, Double-Stranded DNA Repair* Epigenesis, Genetic* Genomic Instability* Germ Cells / enzymology* Histone-Lysine N-Methyltransferase / metabolism* Histones / metabolism Nuclear Proteins
IF 3.339
Times Cited 7
C.elegans tm1489