Maintenance of Genome Integrity by Mi2 Homologs CHD-3 and LET-418 in Caenorhabditis elegans

Abstract

Meiotic recombination depends upon the tightly coordinated regulation of chromosome dynamics and is essential for the production of haploid gametes. Central to this process is the formation and repair of meiotic double-stranded breaks (DSBs), which must take place within the constraints of a specialized chromatin architecture. Here, we demonstrate a role for the nucleosome remodeling and deacetylase (NuRD) complex in orchestrating meiotic chromosome dynamics in Caenorhabditis elegans. Our data reveal that the conserved Mi2 homologs Chromodomain helicase DNA binding protein (CHD-3) and its paralog LET-418 facilitate meiotic progression by ensuring faithful repair of DSBs through homologous recombination. We discovered that loss of either CHD-3 or LET-418 results in elevated p53-dependent germline apoptosis, which relies on the activation of the conserved checkpoint kinase CHK-1. Consistent with these findings, chd-3 and let-418 mutants produce a reduced number of offspring, indicating a role for Mi2 in forming viable gametes. When Mi2 function is compromised, persisting recombination intermediates are detected in late pachytene nuclei, indicating a failure in the timely repair of DSBs. Intriguingly, our data indicate that in Mi2 mutant germ lines, a subset of DSBs are repaired by non-homologous end joining, which manifests as chromosomal fusions.We find that meiotic defects are exacerbated in Mi2 mutants lacking CKU-80, as evidenced by increased recombination intermediates, corpses, and defects in chromosomal integrity. Taken together, our findings support a model wherein the C. elegans Mi2 complex maintains genomic integrity through reinforcement of a chromatin landscape suitable for homology-driven repair mechanisms.4

Overlapping and non-overlapping roles of the class-I histone deacetylase-1 corepressors LET-418, SIN-3, and SPR-1 in Caenorhabditis elegans embryonic development

“…2). The embryonic lethality of hda-1(RNAi) and sin-3(tm1276) mutants was consistent with the findings of previous reports, whereas the embryonic lethality of the let-418(n3536) strain under semi-permissive conditions (maintained at 20 °C) was inconsistent (Beurton et al 2019;Shi and Mello 1998;Turcotte et al 2018). Overall, relative mRNA expression levels and embryonic lethality rates indicate that hda-1, sin-3, let-418, and spr-1 play a role in C. elegans embryogenesis.…”

Locus-specific paramutation in Zea mays is maintained by a PICKLE-like chromodomain helicase DNA-binding 3 protein controlling development and male gametophyte function

“…Although two C . elegans CHD3s, CHD-3 and LET-418, are required for gamete viability [ 89 ], CHD3’s roles in gamete transmission were previously unknown. CHD3a is one of only a few known proteins which when disrupted lead to male transmission ratio distortions.…”

Neonicotinoid-containing insecticide disruption of growth, locomotion, and fertility in Caenorhabditis elegans

“…To assess fertility, wild-type N2, ced-1:GFP, bus-17, and vit-5 worms were staged as L4 larvae and picked 1 worm per plate. Brood size analysis was conducted as described in [52]. Briefly, L4 hermaphrodite worms were transferred to new plates approximately every 24 hours over the course of 3 days.…”