| RRC ID |
53960
|
| 著者 |
Hong Y, Sonneville R, Wang B, Scheidt V, Meier B, Woglar A, Demetriou S, Labib K, Jantsch V, Gartner A.
|
| タイトル |
LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during late mitosis.
|
| ジャーナル |
Nat Commun
|
| Abstract |
Faithful chromosome segregation and genome maintenance requires the removal of all DNA bridges that physically link chromosomes before cells divide. Using C. elegans embryos we show that the LEM-3/Ankle1 nuclease defines a previously undescribed genome integrity mechanism by processing DNA bridges right before cells divide. LEM-3 acts at the midbody, the structure where abscission occurs at the end of cytokinesis. LEM-3 localization depends on factors needed for midbody assembly, and LEM-3 accumulation is increased and prolonged when chromatin bridges are trapped at the cleavage plane. LEM-3 locally processes chromatin bridges that arise from incomplete DNA replication, unresolved recombination intermediates, or the perturbance of chromosome structure. Proper LEM-3 midbody localization and function is regulated by AIR-2/Aurora B kinase. Strikingly, LEM-3 acts cooperatively with the BRC-1/BRCA1 homologous recombination factor to promote genome integrity. These findings provide a molecular basis for the suspected role of the LEM-3 orthologue Ankle1 in human breast cancer.
|
| 巻・号 |
9(1)
|
| ページ |
728
|
| 公開日 |
2018-2-20
|
| DOI |
10.1038/s41467-018-03135-w
|
| PII |
10.1038/s41467-018-03135-w
|
| PMID |
29463814
|
| PMC |
PMC5820297
|
| MeSH |
Animals
Caenorhabditis elegans / embryology
Caenorhabditis elegans / enzymology*
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Chromatin / genetics
Chromatin / metabolism*
Cytokinesis
DNA / genetics
DNA / metabolism
DNA Replication
Endodeoxyribonucleases / genetics
Endodeoxyribonucleases / metabolism*
Mitosis*
|
| IF |
12.121
|
| 引用数 |
9
|
| リソース情報 |
| 線虫 |
tm3468 |
