LINC complexes promote homologous recombination in part through inhibition of nonhomologous end joining.
LINC complexes promote homologous recombination in part through inhibition of nonhomologous end joining.
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DOI：
10.1083/jcb.201604112
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发表时间：
2016-12-19
期刊：
影响因子：
--
通讯作者：
Engebrecht J
中科院分区：
文献类型：
--
作者：
Lawrence KS;Tapley EC;Cruz VE;Li Q;Aung K;Hart KC;Schwartz TU;Starr DA;Engebrecht J
DNA修复对基因组的完整性至关重要。Lawrence等人揭示了一种新型复合物的作用，该复合物将细胞核与微管连接起来，通过抑制易错的非同源末端连接和促进同源重组来促进准确修复。秀丽隐杆线虫SUN结构域蛋白，即SUN-84，在索马的核迁移和锚定中起作用。我们发现了一个新的作用，在DNA损伤修复和减数分裂重组的α-84。缺失RAD-84导致重组酶RAD-51的装载和分解缺陷。与范可尼贫血（FA）基因突变相似，unc-84突变体和缺失Sun-1的人细胞对DNA交联剂敏感，并且通过非同源末端连接（NHEJ）的失活来挽救敏感性。FAN-84还将FA核酸酶FAN-1募集到核质中，这表明FAN-84既改变了NHEJ的修复程度，又促进了FAN-1对交联的处理。KASH-84与KASH蛋白质ZYG-12相互作用，用于DNA损伤修复。此外，微管网络和与核骨架的相互作用对于修复是重要的，这表明需要核骨架和细胞骨架（LINC）复合物的功能性接头。我们提出LINC复合物通过抑制NHEJ和促进染色体断裂位点的同源重组在DNA修复中起保守作用。
DNA repair is critical for genome integrity. Lawrence et al. reveal a role for a novel complex that links the nucleus to microtubules to promote accurate repair through both inhibition of error-prone nonhomologous end joining and promotion of homologous recombination. The Caenorhabditis elegans SUN domain protein, UNC-84, functions in nuclear migration and anchorage in the soma. We discovered a novel role for UNC-84 in DNA damage repair and meiotic recombination. Loss of UNC-84 leads to defects in the loading and disassembly of the recombinase RAD-51. Similar to mutations in Fanconi anemia (FA) genes, unc-84 mutants and human cells depleted of Sun-1 are sensitive to DNA cross-linking agents, and sensitivity is rescued by the inactivation of nonhomologous end joining (NHEJ). UNC-84 also recruits FA nuclease FAN-1 to the nucleoplasm, suggesting that UNC-84 both alters the extent of repair by NHEJ and promotes the processing of cross-links by FAN-1. UNC-84 interacts with the KASH protein ZYG-12 for DNA damage repair. Furthermore, the microtubule network and interaction with the nucleoskeleton are important for repair, suggesting that a functional linker of nucleoskeleton and cytoskeleton (LINC) complex is required. We propose that LINC complexes serve a conserved role in DNA repair through both the inhibition of NHEJ and the promotion of homologous recombination at sites of chromosomal breaks.
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影响因子：
19
作者：
Ceccaldi R;Rondinelli B;D'Andrea AD
通讯作者：
D'Andrea AD
影响因子：
64.5
作者：
Chikashige, Y;Tsutsumi, C;Hiraoka, Y
通讯作者：
Hiraoka, Y
影响因子：
11.8
作者：
Colaiácovo, MP;MacQueen, AJ;Villeneuve, AM
通讯作者：
Villeneuve, AM
DOI：
10.1038/nrc3088
发表时间：
2011-06-24
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
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影响因子：
7.7
作者：
Adamo, Adele;Montemauri, Paolo;La Volpe, Adriana
通讯作者：
La Volpe, Adriana