LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during late mitosis.
LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during late mitosis.
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DOI：
10.1038/s41467-018-03135-w
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发表时间：
2018-02-20
影响因子：
16.6
通讯作者：
Gartner A
中科院分区：
文献类型：
--
作者：
Hong Y;Sonneville R;Wang B;Scheidt V;Meier B;Woglar A;Demetriou S;Labib K;Jantsch V;Gartner A
忠实的染色体分离和基因组维护需要在细胞分裂之前移除所有物理连接染色体的DNA桥。使用线虫胚胎，我们证明了LEM-3/Ankle1核酸酶通过在细胞分裂前处理DNA桥来定义以前未描述的基因组完整性机制。LEM-3在中体起作用，该结构在胞质分裂结束时发生脱落。LEM-3的定位取决于中体组装所需的因素，当染色质桥被捕获在裂解面时，LEM-3的积累增加和延长。LEM-3在局部处理染色质桥，这些桥是由于不完整的DNA复制、未分解的重组中间产物或染色体结构的扰动而产生的。适当的LEM-3中体定位和功能由AIR-2/Aurora B激酶调节。引人注目的是，LEM-3与BRC-1/BRCA1同源重组因子协同作用，促进基因组完整性。这些发现为LEM-3同源基因Ankle1在人类乳腺癌中的可疑作用提供了分子基础。染色体分离和基因组维护需要在细胞分裂前移除连接染色体的DNA桥。在这里，作者证明了LEM-3/Ankle1核酸酶在细胞分裂之前处理DNA桥，并定义了以前未描述的基因组完整性机制。
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. Chromosome segregation and genome maintenance require the removal of DNA bridges that link chromosomes just before cells divide. Here the authors show that the LEM-3/Ankle1 nuclease processes DNA bridges before cells divide and define a previously undescribed genome integrity mechanism.
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影响因子：
4.5
作者：
Hong Y;Sonneville R;Agostinho A;Meier B;Wang B;Blow JJ;Gartner A
通讯作者：
Gartner A
影响因子：
4
作者：
Brachner A;Braun J;Ghodgaonkar M;Castor D;Zlopasa L;Ehrlich V;Jiricny J;Gotzmann J;Knasmüller S;Foisner R
通讯作者：
Foisner R
影响因子：
4.5
作者：
Agostinho A;Meier B;Sonneville R;Jagut M;Woglar A;Blow J;Jantsch V;Gartner A
通讯作者：
Gartner A
影响因子：
9.2
作者：
Bembenek, Joshua N.;Verbrugghe, Koen J. C.;Khanikar, Jayshree;Csankovszki, Gyoergyi;Chan, Raymond C.
通讯作者：
Chan, Raymond C.
影响因子：
3.8
作者：
Matos, Joao;West, Stephen C.
通讯作者：
West, Stephen C.