Dormant origins and fork protection mechanisms rescue sister forks arrested by transcription.
Dormant origins and fork protection mechanisms rescue sister forks arrested by transcription.
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DOI：
10.1093/nar/gkx945
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发表时间：
2018-02-16
影响因子：
14.9
通讯作者：
Liberi G
中科院分区：
文献类型：
--
作者：
Brambati A;Zardoni L;Achar YJ;Piccini D;Galanti L;Colosio A;Foiani M;Liberi G
酵母RNA/DNA解旋酶Sen 1（Senataxin）在人类中通过去除RNA-DNA杂合体来保持遇到转录的复制叉的完整性。在这里，我们表明，在sen 1突变体中，当复制叉与转录正面冲突时，其结果是，在同一复制子内以相反方向移动的姐妹叉的进展也受到损害。因此，当两个分叉中的一个被转录捕获时，姐妹分叉仍然是耦合的，这与分叉遇到双链断裂时所经历的命运不同。我们还表明，休眠的复制起点被激活，以确保在附近的叉转录逮捕的DNA合成。休眠起点的激发不受复制检查点的抑制，相反，如果它们不能被被动复制及时灭活，则休眠起点被激发。在sen 1突变体中，Mre 11和Mrc 1-Ctf 4复合物保护被转录阻止的叉免受Exo 1核酸酶介导的加工。因此，一个无害的迎面复制-转录冲突的解决需要微调的起源射击和协调之间的Sen 1，Exo 1，Mre 11和Mrc 1-Ctf 4复合物。
The yeast RNA/DNA helicase Sen1, Senataxin in human, preserves the integrity of replication forks encountering transcription by removing RNA-DNA hybrids. Here we show that, in sen1 mutants, when a replication fork clashes head-on with transcription is arrested and, as a consequence, the progression of the sister fork moving in the opposite direction within the same replicon is also impaired. Therefore, sister forks remain coupled when one of the two forks is arrested by transcription, a fate different from that experienced by forks encountering Double Strand Breaks. We also show that dormant origins of replication are activated to ensure DNA synthesis in the proximity to the forks arrested by transcription. Dormant origin firing is not inhibited by the replication checkpoint, rather dormant origins are fired if they cannot be timely inactivated by passive replication. In sen1 mutants, the Mre11 and Mrc1–Ctf4 complexes protect the forks arrested by transcription from processing mediated by the Exo1 nuclease. Thus, a harmless head-on replication-transcription clash resolution requires the fine-tuning of origin firing and coordination among Sen1, Exo1, Mre11 and Mrc1–Ctf4 complexes.
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影响因子：
64.8
作者：
Bartkova, Jirina;Rezaei, Nousin;Gorgoulis, Vassilis G.
通讯作者：
Gorgoulis, Vassilis G.
影响因子：
64.8
作者：
Di Micco, Raffaella;Fumagalli, Marzia;di Fagagna, Fabrizio d'Adda
通讯作者：
di Fagagna, Fabrizio d'Adda
影响因子：
64.5
作者：
Barlow JH;Faryabi RB;Callén E;Wong N;Malhowski A;Chen HT;Gutierrez-Cruz G;Sun HW;McKinnon P;Wright G;Casellas R;Robbiani DF;Staudt L;Fernandez-Capetillo O;Nussenzweig A
通讯作者：
Nussenzweig A
影响因子：
64.8
作者：
Ray Chaudhuri A;Callen E;Ding X;Gogola E;Duarte AA;Lee JE;Wong N;Lafarga V;Calvo JA;Panzarino NJ;John S;Day A;Crespo AV;Shen B;Starnes LM;de Ruiter JR;Daniel JA;Konstantinopoulos PA;Cortez D;Cantor SB;Fernandez-Capetillo O;Ge K;Jonkers J;Rottenberg S;Sharan SK;Nussenzweig A
通讯作者：
Nussenzweig A
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.