Reference - Detail
| RRC ID | 76106 |
|---|---|
| Author | Zhang X, Tian S, Beese-Sims SE, Chen J, Shin N, Colaiácovo MP, Kim HM. |
| Title | Histone demethylase AMX-1 is necessary for proper sensitivity to interstrand crosslink DNA damage. |
| Journal | PLoS Genet |
| Abstract |
Histone methylation is dynamically regulated to shape the epigenome and adjust central nuclear processes including transcription, cell cycle control and DNA repair. Lysine-specific histone demethylase 2 (LSD2) has been implicated in multiple types of human cancers. However, its functions remain poorly understood. This study investigated the histone demethylase LSD2 homolog AMX-1 in C. elegans and uncovered a potential link between H3K4me2 modulation and DNA interstrand crosslink (ICL) repair. AMX-1 is a histone demethylase and mainly localizes to embryonic cells, the mitotic gut and sheath cells. Lack of AMX-1 expression resulted in embryonic lethality, a decreased brood size and disorganized premeiotic tip germline nuclei. Expression of AMX-1 and of the histone H3K4 demethylase SPR-5 is reciprocally up-regulated upon lack of each other and the mutants show increased H3K4me2 levels in the germline, indicating that AMX-1 and SPR-5 regulate H3K4me2 demethylation. Loss of AMX-1 function activates the CHK-1 kinase acting downstream of ATR and leads to the accumulation of RAD-51 foci and increased DNA damage-dependent apoptosis in the germline. AMX-1 is required for the proper expression of mismatch repair component MutL/MLH-1 and sensitivity against ICLs. Interestingly, formation of ICLs lead to ubiquitination-dependent subcellular relocalization of AMX-1. Taken together, our data suggest that AMX-1 functions in ICL repair in the germline. |
| Volume | 17(7) |
| Pages | e1009715 |
| Published | 2021-7-1 |
| DOI | 10.1371/journal.pgen.1009715 |
| PII | PGENETICS-D-21-00389 |
| PMID | 34329293 |
| PMC | PMC8357103 |
| MeSH | Animals Animals, Genetically Modified Caenorhabditis elegans Caenorhabditis elegans Proteins Cell Nucleus / metabolism DNA Damage / genetics DNA Repair / genetics* DNA Repair / physiology Germ Cells / metabolism Histone Demethylases / metabolism* Histone Demethylases / physiology Histones / genetics Methylation Protein Processing, Post-Translational / genetics Ubiquitination |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 4 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm2176 tm2181 |