The MRN complex and topoisomerase IIIa-RMI1/2 synchronize DNA resection motor proteins.
The MRN complex and topoisomerase IIIa-RMI1/2 synchronize DNA resection motor proteins.
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DOI：
10.1016/j.jbc.2022.102802
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发表时间：
2023-02
影响因子：
4.8
通讯作者：
Finkelstein, Ilya J.
中科院分区：
文献类型：
--
作者：
Soniat, Michael M.;Nguyen, Giaochau;Kuo, Hung-Che;Finkelstein, Ilya J.
DNA切除-断裂DNA末端的溶核处理-是同源重组的第一步。切除由切除体催化，切除体是一种多酶复合物，包括布卢姆综合征解旋酶（BLM）、DNA 2或核酸外切酶1核酸酶和其他DNA结合蛋白。虽然分子参与者已经知道了十多年，但单个蛋白质如何共同作用以调节DNA切除仍然未知。使用单分子成像，我们表征了MRE 11-RAD 50-NBS 1复合物（MRN）和拓扑异构酶IIIa（TOP 3A）-RMI 1/2在长距离DNA切除过程中的作用。BLM与TOP 3A-RMI 1/2形成BTRR（BLM-TOP 3A-RMI 1/2）复合物（或BLM溶解体）。我们确定TOP 3A-RMI 1/2有助于BLM启动DNA解旋，并与MRN一起沿着刺激DNA 2介导的切除。此外，我们发现，MRN促进BTRR和DNA之间的关联和BLM和DNA 2易位，以防止BLM在切除过程中暂停。总之，这项工作提供了直接观察MRN和DNA 2如何利用BTRR复合物有效地切除DNA，以及TOP 3A-RMI 1/2如何调节BLM的解旋酶活性以促进有效的DNA修复。
DNA resection—the nucleolytic processing of broken DNA ends—is the first step of homologous recombination. Resection is catalyzed by the resectosome, a multienzyme complex that includes bloom syndrome helicase (BLM), DNA2 or exonuclease 1 nucleases, and additional DNA-binding proteins. Although the molecular players have been known for over a decade, how the individual proteins work together to regulate DNA resection remains unknown. Using single-molecule imaging, we characterized the roles of the MRE11–RAD50–NBS1 complex (MRN) and topoisomerase IIIa (TOP3A)–RMI1/2 during long-range DNA resection. BLM partners with TOP3A–RMI1/2 to form the BTRR (BLM–TOP3A–RMI1/2) complex (or BLM dissolvasome). We determined that TOP3A–RMI1/2 aids BLM in initiating DNA unwinding, and along with MRN, stimulates DNA2-mediated resection. Furthermore, we found that MRN promotes the association between BTRR and DNA and synchronizes BLM and DNA2 translocation to prevent BLM from pausing during resection. Together, this work provides direct observation of how MRN and DNA2 harness the BTRR complex to resect DNA efficiently and how TOP3A–RMI1/2 regulates the helicase activity of BLM to promote efficient DNA repair.
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DOI：
10.1021/acs.langmuir.5b02416
发表时间：
2015-09-22
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
--
作者：
Gallardo IF;Pasupathy P;Brown M;Manhart CM;Neikirk DP;Alani E;Finkelstein IJ
通讯作者：
Finkelstein IJ
影响因子：
16.8
作者：
Davies, Sally L.;North, Phillip S.;Hickson, Ian D.
通讯作者：
Hickson, Ian D.
DOI：
10.1073/pnas.1309816110
发表时间：
2013-11-19
影响因子：
11.1
作者：
Cannon, Brian;Kuhnlein, Jeffrey;Paull, Tanya T.
通讯作者：
Paull, Tanya T.
影响因子：
7.2
作者：
Kowalczykowski, Stephen C.
通讯作者：
Kowalczykowski, Stephen C.
影响因子：
14.9
作者：
Daley JM;Chiba T;Xue X;Niu H;Sung P
通讯作者：
Sung P