期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-03135-w
关键词
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资金
- Wellcome Trust [AG 0909444/Z/09/Z, KL 102943/Z/13/Z, 097045/B/11/Z, 097945/B/11/Z]
- MRC [MC_UU_12016/13, MR/K015869/1]
- FWF [VJ SFB-F34]
- Wellcome PhD fellowship
- ISSF
- NIH Office of Research Infrastructure Programs [P40 OD010440]
- BBSRC [BB/J015199/1] Funding Source: UKRI
- MRC [MC_UU_12016/13, MC_UU_00018/4, MR/K015869/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/J015199/1] Funding Source: researchfish
- Cancer Research UK [24558] Funding Source: researchfish
- Medical Research Council [MR/K015869/1, MC_UU_12016/13, MC_UU_00018/4] Funding Source: researchfish
- Wellcome Trust [102943/Z/13/Z] Funding Source: researchfish
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.
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