Persistent DNA damage signaling and DNA polymerase theta promote broken chromosome segregation.
Persistent DNA damage signaling and DNA polymerase theta promote broken chromosome segregation.
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DOI：
10.1083/jcb.202106116
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发表时间：
2021-12-06
期刊：
影响因子：
--
通讯作者：
Fox DT
中科院分区：
文献类型：
--
作者：
Clay DE;Bretscher HS;Jezuit EA;Bush KB;Fox DT
Clay et al. show that cells with DNA breaks that persist into mitosis activate sustained DNA damage signaling, regulated by Fanconi anemia proteins and the alternative end-joining repair protein DNA polymerase θ. This signaling enables broken chromosome segregation and prevents micronuclei. Cycling cells must respond to DNA double-strand breaks (DSBs) to avoid genome instability. Missegregation of chromosomes with DSBs during mitosis results in micronuclei, aberrant structures linked to disease. How cells respond to DSBs during mitosis is incompletely understood. We previously showed that Drosophila melanogaster papillar cells lack DSB checkpoints (as observed in many cancer cells). Here, we show that papillar cells still recruit early acting repair machinery (Mre11 and RPA3) and the Fanconi anemia (FA) protein Fancd2 to DSBs. These proteins persist as foci on DSBs as cells enter mitosis. Repair foci are resolved in a stepwise manner during mitosis. DSB repair kinetics depends on both monoubiquitination of Fancd2 and the alternative end-joining protein DNA polymerase θ. Disruption of either or both of these factors causes micronuclei after DNA damage, which disrupts intestinal organogenesis. This study reveals a mechanism for how cells with inactive DSB checkpoints can respond to DNA damage that persists into mitosis.
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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：
4.8
作者：
Furuta, T;Takemura, H;Pommier, Y
通讯作者：
Pommier, Y
染色体不稳定性通过胞质DNA反应驱动转移。
影响因子：
64.8
作者：
Bakhoum SF;Ngo B;Laughney AM;Cavallo JA;Murphy CJ;Ly P;Shah P;Sriram RK;Watkins TBK;Taunk NK;Duran M;Pauli C;Shaw C;Chadalavada K;Rajasekhar VK;Genovese G;Venkatesan S;Birkbak NJ;McGranahan N;Lundquist M;LaPlant Q;Healey JH;Elemento O;Chung CH;Lee NY;Imielenski M;Nanjangud G;Pe'er D;Cleveland DW;Powell SN;Lammerding J;Swanton C;Cantley LC
通讯作者：
Cantley LC
影响因子：
4.5
作者：
Carvajal-Garcia J;Crown KN;Ramsden DA;Sekelsky J
通讯作者：
Sekelsky J
影响因子：
11.8
作者：
Bretscher HS;Fox DT
通讯作者：
Fox DT