ID3 promotes homologous recombination via non-transcriptional and transcriptional mechanisms and its loss confers sensitivity to PARP inhibition.
ID3 promotes homologous recombination via non-transcriptional and transcriptional mechanisms and its loss confers sensitivity to PARP inhibition.
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DOI：
10.1093/nar/gkab964
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发表时间：
2021-11-18
影响因子：
14.9
通讯作者：
Schmezer P
中科院分区：
文献类型：
--
作者：
Bakr A;Hey J;Sigismondo G;Liu CS;Sadik A;Goyal A;Cross A;Iyer RL;Müller P;Trauernicht M;Breuer K;Lutsik P;Opitz CA;Krijgsveld J;Weichenhan D;Plass C;Popanda O;Schmezer P
DNA结合抑制剂3（ID 3）是限制碱性螺旋-环-螺旋转录因子与其靶DNA序列相互作用的转录调节因子。我们以前报道过ID 3缺失与DNA修复缺陷相关的突变特征有关。在这里，我们证明了ID 3表现出双重作用，以促进DNA双链断裂（DSB）修复，特别是同源重组（HR）。ID 3与MRN复合物和RECQL解旋酶相互作用以激活DSB修复，并且它促进RAD 51加载和HR的下游步骤。此外，ID 3通过调节染色质可及性和转录因子E2 F1的活性来促进HR基因响应电离辐射的表达。一致地，TCGA癌症患者数据的分析表明，低ID 3表达与受损的HR 13 ID 3的损失导致肿瘤细胞对PARP抑制的敏感性，为ID 3缺陷型肿瘤提供了新的治疗机会。ID 3在促进同源重组中的双重作用。
The inhibitor of DNA-binding 3 (ID3) is a transcriptional regulator that limits interaction of basic helix-loop-helix transcription factors with their target DNA sequences. We previously reported that ID3 loss is associated with mutational signatures linked to DNA repair defects. Here we demonstrate that ID3 exhibits a dual role to promote DNA double-strand break (DSB) repair, particularly homologous recombination (HR). ID3 interacts with the MRN complex and RECQL helicase to activate DSB repair and it facilitates RAD51 loading and downstream steps of HR. In addition, ID3 promotes the expression of HR genes in response to ionizing radiation by regulating both chromatin accessibility and activity of the transcription factor E2F1. Consistently, analyses of TCGA cancer patient data demonstrate that low ID3 expression is associated with impaired HR. The loss of ID3 leads to sensitivity of tumor cells to PARP inhibition, offering new therapeutic opportunities in ID3-deficient tumors. Dual role of ID3 in promoting homologous recombination.
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影响因子：
14.9
作者：
Bakr A;Oing C;Köcher S;Borgmann K;Dornreiter I;Petersen C;Dikomey E;Mansour WY
通讯作者：
Mansour WY
影响因子：
16.8
作者：
Berti, Matteo;Chaudhuri, Arnab Ray;Thangavel, Saravanabhavan;Gomathinayagam, Shivasankari;Kenig, Sasa;Vujanovic, Marko;Odreman, Federico;Glatter, Timo;Graziano, Simona;Mendoza-Maldonado, Ramiro;Marino, Francesca;Lucic, Bojana;Biasin, Valentina;Gstaiger, Matthias;Aebersold, Ruedi;Sidorova, Julia M.;Monnat, Raymond J., Jr.;Lopes, Massimo;Vindigni, Alessandro
通讯作者：
Vindigni, Alessandro
影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
通讯作者：
Noushmehr H
影响因子：
64.5
作者：
BENEZRA, R;DAVIS, RL;WEINTRAUB, H
通讯作者：
WEINTRAUB, H
影响因子：
16
作者：
Ciccia A;Elledge SJ
通讯作者：
Elledge SJ