Nuclear lamina dysfunction triggers a germline stem cell checkpoint.
Nuclear lamina dysfunction triggers a germline stem cell checkpoint.
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DOI：
10.1038/s41467-018-06277-z
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发表时间：
2018-09-27
影响因子：
16.6
通讯作者：
Geyer PK
中科院分区：
文献类型：
--
作者：
Barton LJ;Duan T;Ke W;Luttinger A;Lovander KE;Soshnev AA;Geyer PK
LEM结构域（LEM-D）蛋白是核纤层（NL）的保守组分，其通过知之甚少的机制促进干细胞维持。果蝇Emerin同系物Otefin（Ote）是维持生殖系干细胞（GSC）和配子发生所必需的。在这里，我们表明，ote突变体携带生殖细胞特异性的核结构的变化，与GSC的损失。引人注目的是，我们发现GSC死亡和配子发生都是通过DNA损伤反应（DDR）激酶ATR和Chk 2的失活来挽救的。尽管生殖系检查点来自DDR途径的组分，但GSC检查点的遗传和细胞学特征与经典途径不同。相反，NL的结构变形与检查点激活相关。尽管非常正常的卵子发生，挽救的卵母细胞不支持胚胎发生。总之，这些数据表明，由Otefin损失引起的NL功能障碍触发了GSC特异性检查点，有助于维持配子质量。Otefin是果蝇生殖干细胞存活所需的核纤层蛋白。在这里，作者表明，由于Otefin的丢失导致的核纤层功能障碍激活了由ATR和Chk 2激酶介导的DNA损伤独立的生殖干细胞特异性检查点，这确保了健康的配子传递给下一代。
LEM domain (LEM-D) proteins are conserved components of the nuclear lamina (NL) that contribute to stem cell maintenance through poorly understood mechanisms. The Drosophila emerin homolog Otefin (Ote) is required for maintenance of germline stem cells (GSCs) and gametogenesis. Here, we show that ote mutants carry germ cell-specific changes in nuclear architecture that are linked to GSC loss. Strikingly, we found that both GSC death and gametogenesis are rescued by inactivation of the DNA damage response (DDR) kinases, ATR and Chk2. Whereas the germline checkpoint draws from components of the DDR pathway, genetic and cytological features of the GSC checkpoint differ from the canonical pathway. Instead, structural deformation of the NL correlates with checkpoint activation. Despite remarkably normal oogenesis, rescued oocytes do not support embryogenesis. Taken together, these data suggest that NL dysfunction caused by Otefin loss triggers a GSC-specific checkpoint that contributes to maintenance of gamete quality. Otefin is a nuclear lamina protein required for survival of Drosophila germ stem cells. Here the authors show that nuclear lamina dysfunction resulting from loss of Otefin activates a DNA damage-independent germ stem cell-specific checkpoint, mediated by the ATR and Chk2 kinases, which ensures that healthy gametes are passed on to the next generation.
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影响因子：
23.9
作者：
Ables, Elizabeth T.;Drummond-Barbosa, Daniela
通讯作者：
Drummond-Barbosa, Daniela
影响因子：
1.7
作者：
Ciapponi, L.;Cenci, G.
通讯作者：
Cenci, G.
影响因子：
64.5
作者：
Burgess RC;Misteli T
通讯作者：
Misteli T
DOI：
10.1007/s10577-017-9556-x
发表时间：
2017-10
期刊：
Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology
影响因子：
--
作者：
Deniaud E;Lemaître C;Boyle S;Bickmore WA
通讯作者：
Bickmore WA
DOI：
10.1083/jcb.141.1.5
发表时间：
1998-04-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fung JC;Marshall WF;Dernburg A;Agard DA;Sedat JW
通讯作者：
Sedat JW