A senataxin-associated exonuclease SAN1 is required for resistance to DNA interstrand cross-links.
A senataxin-associated exonuclease SAN1 is required for resistance to DNA interstrand cross-links.
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DOI：
10.1038/s41467-018-05008-8
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发表时间：
2018-07-03
影响因子：
16.6
通讯作者：
Macara IG
中科院分区：
文献类型：
--
作者：
Andrews AM;McCartney HJ;Errington TM;D'Andrea AD;Macara IG
链间DNA交联（ICL）阻断复制和转录，通常通过范可尼贫血（FA）途径修复。然而，对ICLs的FA非依赖性修复机制仍知之甚少。在这里，我们报告了一个以前未知的蛋白质，SAN 1，作为一个5′核酸外切酶，其作用独立于FA途径，以响应ICLs。HeLa细胞和小鼠胚胎成纤维细胞中SAN 1的缺失导致对ICL的敏感性，这可以通过野生型而不是核酸酶死亡的SAN 1的重新表达来防止。SAN 1缺失导致DNA损伤和放射状染色体形成后，用丝裂霉素C，phenocopying缺陷的FA途径。然而，SAN 1缺失与FANCD 2（FA通路的核心组分）不具有上位性。出乎意料的是，SAN 1与Senataxin（SETX）结合，Senataxin是一种分解R环的RNA/DNA解旋酶。SAN 1-SETX结合通过ICL增加，并且是防止交联敏感性所必需的。我们建议SAN 1功能与SETX在一个必要的途径耐ICLs。当DNA链间交联损伤发生时，它会导致复制和转录的中断。在这里，作者鉴定了FAM 120 B/SAN 1，这是一种参与链间交联修复过程的5′核酸外切酶，独立于范可尼贫血途径。
Interstrand DNA cross-links (ICLs) block both replication and transcription, and are commonly repaired by the Fanconi anemia (FA) pathway. However, FA-independent repair mechanisms of ICLs remain poorly understood. Here we report a previously uncharacterized protein, SAN1, as a 5′ exonuclease that acts independently of the FA pathway in response to ICLs. Deletion of SAN1 in HeLa cells and mouse embryonic fibroblasts causes sensitivity to ICLs, which is prevented by re-expression of wild type but not nuclease-dead SAN1. SAN1 deletion causes DNA damage and radial chromosome formation following treatment with Mitomycin C, phenocopying defects in the FA pathway. However, SAN1 deletion is not epistatic with FANCD2, a core FA pathway component. Unexpectedly, SAN1 binds to Senataxin (SETX), an RNA/DNA helicase that resolves R-loops. SAN1-SETX binding is increased by ICLs, and is required to prevent cross-link sensitivity. We propose that SAN1 functions with SETX in a pathway necessary for resistance to ICLs. When DNA interstrand cross-links damage occurs, it causes disruption of replication and transcription. Here the authors identify FAM120B/SAN1, a 5′ exonuclease involved in the repair process of Interstrand Crosslinks independently of the Fanconi Anemia pathway.
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影响因子：
16
作者：
Hodskinson, Michael R. G.;Silhan, Jan;Crossan, Gerry P.;Garaycoechea, Juan I.;Mukherjee, Shivam;Johnson, Christopher M.;Schaerer, Orlando D.;Patel, Ketan J.
通讯作者：
Patel, Ketan J.
影响因子：
9.8
作者：
Bogliolo, Massimo;Schuster, Beatrice;Surralles, Jordi
通讯作者：
Surralles, Jordi
SLX1和MUS81-EME1核酸酶对Holliday连接分辨率和DNA修复的合作控制。
影响因子：
16
作者：
Castor, Dennis;Nair, Nidhi;Declais, Anne-Cecile;Lachaud, Christophe;Toth, Rachel;Macartney, Thomas J.;Lilley, David M. J.;Arthur, J. Simon C.;Rouse, John
通讯作者：
Rouse, John
影响因子：
16
作者：
Hatchi, Elodie;Skourti-Stathaki, Konstantina;Ventz, Steffen;Pinello, Luca;Yen, Angela;Kamieniarz-Gdula, Kinga;Dimitrov, Stoil;Pathania, Shailja;McKinney, Kristine M.;Eaton, Matthew L.;Kellis, Manolis;Hill, Sarah J.;Parmigiani, Giovanni;Proudfoot, Nicholas J.;Livingston, David M.
通讯作者：
Livingston, David M.
影响因子：
5.3
作者：
Ishiai, M;Kimura, M;Takata, M
通讯作者：
Takata, M