Sister chromatid exchanges induced by perturbed replication can form independently of BRCA1, BRCA2 and RAD51.
Sister chromatid exchanges induced by perturbed replication can form independently of BRCA1, BRCA2 and RAD51.
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DOI：
10.1038/s41467-022-34519-8
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发表时间：
2022-11-07
影响因子：
16.6
通讯作者：
van Vugt, Marcel A. T. M.
中科院分区：
文献类型：
--
作者：
Heijink, Anne Margriet;Stok, Colin;Porubsky, David;Manolika, Eleni Maria;de Kanter, Jurrian K.;Kok, Yannick P.;Everts, Marieke;de Boer, H. Rudolf;Audrey, Anastasia;Bakker, Femke J.;Wierenga, Elles;Tijsterman, Marcel;Guryev, Victor;Spierings, Diana C. J.;Knipscheer, Puck;van Boxtel, Ruben;Chaudhuri, Arnab Ray;Lansdorp, Peter M.;van Vugt, Marcel A. T. M.
姐妹染色单体交换（SCE）是联合DNA分子解析的产物，被认为是通过同源重组（HR）形成的。事实上，照射后的SCE诱导需要典型的HR因子BRCA 1，BRCA 2和RAD 51。相反，复制阻断剂，包括PARP抑制剂，诱导SCE独立于BRCA 1，BRCA 2和RAD 51。PARP标记诱导的SCE在难以复制的基因组区域富集，包括常见的脆性位点（CFS）。PARP标记物诱导的复制损伤被传递到有丝分裂中，这表明SCE可以起源于复制不足的DNA的有丝分裂加工。蛋白质组学分析揭示了DNA聚合酶θ（POLQ）的有丝分裂招募到合成DNA末端。POLQ失活导致HR缺陷细胞中PARP抑制后SCE数量减少和严重的染色体断裂。因此，癌症基因组中CFS的分析揭示了频繁的等位基因缺失，两侧是POLQ介导的修复的特征。结合，我们表明PARP抑制产生复制不足的DNA，这是有丝分裂过程中加工成SCE，独立于典型的HR因素。姐妹染色单体交换（SCE）被认为是同源重组修复的产物。作者表明，SCE可以独立于同源重组，由于在有丝分裂过程中的复制中间体的加工。
Sister chromatid exchanges (SCEs) are products of joint DNA molecule resolution, and are considered to form through homologous recombination (HR). Indeed, SCE induction upon irradiation requires the canonical HR factors BRCA1, BRCA2 and RAD51. In contrast, replication-blocking agents, including PARP inhibitors, induce SCEs independently of BRCA1, BRCA2 and RAD51. PARP inhibitor-induced SCEs are enriched at difficult-to-replicate genomic regions, including common fragile sites (CFSs). PARP inhibitor-induced replication lesions are transmitted into mitosis, suggesting that SCEs can originate from mitotic processing of under-replicated DNA. Proteomics analysis reveals mitotic recruitment of DNA polymerase theta (POLQ) to synthetic DNA ends. POLQ inactivation results in reduced SCE numbers and severe chromosome fragmentation upon PARP inhibition in HR-deficient cells. Accordingly, analysis of CFSs in cancer genomes reveals frequent allelic deletions, flanked by signatures of POLQ-mediated repair. Combined, we show PARP inhibition generates under-replicated DNA, which is processed into SCEs during mitosis, independently of canonical HR factors. Sister chromatid exchanges (SCEs) are considered to be products of homologous recombination repair. The authors show that SCEs can arise independently of homologous recombination due to processing of replication intermediates during mitosis.
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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：
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
DOI：
10.4161/15384101.2014.977067
发表时间：
2015
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Benada J;Burdová K;Lidak T;von Morgen P;Macurek L
通讯作者：
Macurek L
影响因子：
7.7
作者：
Claussin C;Porubský D;Spierings DC;Halsema N;Rentas S;Guryev V;Lansdorp PM;Chang M
通讯作者：
Chang M
影响因子：
16
作者：
Dias, Mariana Paes;Tripathi, Vivek;van der Heijden, Ingrid;Cong, Ke;Manolika, Eleni-Maria;Bhin, Jinhyuk;Gogola, Ewa;Galanos, Panagiotis;Annunziato, Stefano;Lieftink, Cor;Andujar-Sanchez, Miguel;Chakrabarty, Sanjiban;Smith, Graeme C. M.;van de Ven, Marieke;Beijersbergen, Roderick L.;Bartkova, Jirina;Rottenberg, Sven;Cantor, Sharon;Bartek, Jiri;Chaudhuri, Arnab Ray;Jonkers, Jos
通讯作者：
Jonkers, Jos