DNA Repair最新文献_第3页

Innate immune sensing and signaling: Co-opted for genome surveillance? Implications for tumorigenesis 先天免疫感知和信号传导：基因组监测的增选？对肿瘤发生的影响

IF 2.7 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair

Pub Date : 2025-09-01 DOI: 10.1016/j.dnarep.2025.103890

Hexiao Wang, John H.J. Petrini

Innate immune signaling is traditionally associated with the response to pathogenic infection. However, emerging evidence suggests that nuclear innate immune sensors and their downstream pathways may also serve as a critical mechanism for genome surveillance. This review explores a model in which DNA sensors such as mouse IFI204 and IFI205 (IFI16 in humans) localize to replication forks, where they detect endogenous aberrant DNA structures and initiate an interferon-stimulated gene (ISG) transcriptional program. A key output of this transcriptional program is ISG15, which we find conjugated to fork-associated proteins and facilitates recruitment of the replication fork protection complex, thereby stabilizing replication forks under physiological conditions. We discuss how nuclear innate immune sensors mediate replication stress sensing and examine the broad consequences of downstream ISG transcription across diverse contexts—including its impact on genome stability and its dual roles in modulating tumor cell behavior and the tumor microenvironment. These findings suggest that the innate immune system, through its nuclear DNA sensing arm, may be evolutionarily co-opted for genome surveillance and may influence tumor initiation and therapy resistance. Understanding how innate immune signaling intersects with replication stress could offer mechanistic insights into tumor development and reveal novel therapeutic targets.

先天免疫信号通常与致病性感染的反应有关。然而，新出现的证据表明，核先天免疫传感器及其下游途径也可能作为基因组监测的关键机制。这篇综述探讨了一种模型，其中DNA传感器如小鼠IFI204和IFI205（人类IFI16）定位于复制叉，在那里它们检测内源性异常DNA结构并启动干扰素刺激基因（ISG）转录程序。该转录程序的一个关键输出是ISG15，我们发现它与叉相关蛋白结合，促进复制叉保护复合体的招募，从而在生理条件下稳定复制叉。我们讨论了核先天免疫传感器如何介导复制应激感应，并研究了下游ISG转录在不同背景下的广泛影响，包括其对基因组稳定性的影响及其在调节肿瘤细胞行为和肿瘤微环境中的双重作用。这些发现表明，先天免疫系统通过其核DNA传感臂，可能在进化中被用于基因组监测，并可能影响肿瘤的发生和治疗耐药性。了解先天免疫信号如何与复制应激相交，可以为肿瘤发展提供机制见解，并揭示新的治疗靶点。

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引用次数: 0

DNA damage response inhibitors in cancer therapy: Mechanisms, clinical development, and combination strategies DNA损伤反应抑制剂在癌症治疗中的应用：机制、临床发展和联合策略

IF 2.7 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair

Pub Date : 2025-08-21 DOI: 10.1016/j.dnarep.2025.103887

Seon-gyeong Lee , Jinwoo Kim , Euihwan Jeong , Kyungjae Myung

Impaired genomic stability is a hallmark of many cancers, with the DNA damage response (DDR) mechanisms serving as critical safeguards for maintaining genomic integrity. These intricate DDR networks, encompassing various DNA repair and damage checkpoint pathways, are essential for regulating the cell cycle, immune responses, and apoptosis. Notably, defects in DDR pathways, particularly those involving BRCA1/2 mutations, present exploitable vulnerabilities for targeted therapies such as PARP inhibitors (PARPi). This review explores the mechanisms by which PARPi function as cancer therapies, focusing on their ability to inhibit DNA repair processes and induce tumor cell death. It also examines the current landscape of PARPi clinical trials and their application across various cancer types. In addition, we discuss emerging DDR inhibitors, including CHK1/2, ATR, ATM, RAD51, APE1, and WEE1, many of which act by inhibiting DNA repair and damage checkpoints. These inhibitors selectively target malignant cells that are deficient in checkpoint function, thereby inducing replication stress and mitotic catastrophe. While DDR inhibitors hold great potential as standalone therapies or in combination with chemotherapy, immunotherapy, and radiation, challenges persist, including overlapping toxicities and damage to healthy tissues. This review aims to illuminate the rapidly advancing field of DDR-based targeted cancer therapies, emphasizing their potential to revolutionize treatment approaches and improve patient outcomes.

基因组稳定性受损是许多癌症的标志，DNA损伤反应（DDR）机制是维持基因组完整性的关键保障。这些复杂的DDR网络包含各种DNA修复和损伤检查点通路，对调节细胞周期、免疫反应和细胞凋亡至关重要。值得注意的是，DDR通路中的缺陷，特别是那些涉及BRCA1/2突变的缺陷，为PARP抑制剂（PARPi）等靶向治疗提供了可利用的漏洞。这篇综述探讨了PARPi作为癌症治疗的机制，重点是它们抑制DNA修复过程和诱导肿瘤细胞死亡的能力。它还检查了PARPi临床试验的现状及其在各种癌症类型中的应用。此外，我们还讨论了新兴的DDR抑制剂，包括CHK1/2、ATR、ATM、RAD51、APE1和WEE1，其中许多抑制剂通过抑制DNA修复和损伤检查点起作用。这些抑制剂选择性地靶向检查点功能缺陷的恶性细胞，从而诱导复制应激和有丝分裂灾难。虽然DDR抑制剂作为单独治疗或与化疗、免疫治疗和放射联合治疗具有巨大潜力，但挑战仍然存在，包括重叠毒性和对健康组织的损害。本综述旨在阐明快速发展的基于ddr的靶向癌症治疗领域，强调其革命性治疗方法和改善患者预后的潜力。

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引用次数: 0

Insight into meiotic DNA end resection: Mechanisms and regulation 洞察减数分裂DNA末端切除：机制和调控

IF 2.7 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair

Pub Date : 2025-08-15 DOI: 10.1016/j.dnarep.2025.103886

Soonjoung Kim , Hasan F. Alnaser , Scott Keeney , Hajime Murakami

Meiosis generates reproductive cells with a reduced genome complement, with most species using homologous recombination to promote accurate meiotic chromosome segregation and to generate genetic diversity among offspring. A critical step in homologous recombination is DNA end resection, in which DNA double-strand breaks (DSBs) are processed by nucleases to yield the 3′ single-stranded DNA (ssDNA) needed for homology search and strand invasion. DSB resection in nonmeiotic contexts has been extensively studied, but meiotic resection is less well understood. We provide here a review of studies elucidating the mechanism and regulation of resection during meiosis, covering similarities and differences from resection in mitotically dividing cells. The nucleases that carry out resection are discussed, along with resection-modulating factors such as DNA damage signaling and chromatin structure. We focus on the budding yeast Saccharomyces cerevisiae and on mouse, for which the most information is currently available, but also describe studies in other species that point to evolutionary conservation or divergence in this key process needed for genome integrity in the germline.

减数分裂产生的生殖细胞具有较少的基因组补体，大多数物种使用同源重组来促进精确的减数分裂染色体分离并在后代中产生遗传多样性。同源重组的关键步骤是DNA末端切除，其中DNA双链断裂（dsb）由核酸酶加工产生同源搜索和链入侵所需的3 '单链DNA （ssDNA）。非减数分裂背景下的DSB切除已被广泛研究，但减数分裂切除尚不清楚。我们在此综述了减数分裂过程中切除的机制和调控，包括与有丝分裂细胞中切除的异同。讨论了进行切除的核酸酶，以及切除调节因子，如DNA损伤信号和染色质结构。我们主要关注出芽酵母（Saccharomyces cerevisiae）和小鼠，这是目前可用的信息最多的，但也描述了其他物种的研究，这些研究指出了进化保护或分化在种系基因组完整性所需的关键过程中。

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引用次数: 0

Proofreading exonuclease activities of Polδ and Polε differentially contribute to the removal of chain-terminating nucleoside analogs 校对Polδ和Polε的核酸外切酶活性对链终止核苷类似物的去除有不同的作用

IF 2.7 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair

Pub Date : 2025-08-14 DOI: 10.1016/j.dnarep.2025.103885

Eri Nishizawa , Hiromori Ohkubo , Ryotaro Kawasumi , Masataka Tsuda , Kouji Hirota

Chain-terminating nucleoside analogs (CTNAs) are incorporated into genome during replication by replicative polymerase delta (Polδ) and epsilon (Polε), then inhibit DNA synthesis by preventing subsequent polymerization. The proofreading exonuclease activity of Polε removes the incorporated CTNAs, thereby contributing to cellular tolerance to these drugs. However, the contribution of Polδ’s proofreading exonuclease activity has not been clarified, nor has the relationship between Polδ and Polε been well understood. We here show that Polδ’s exonuclease activity contributes to the cellular tolerance to CTNAs, with the role of Polδ and Polε exonucleases differing depending on the kinds of CTNAs. We tested the sensitivity of POLD1^exo−/+ cells to a CTNA, Ara-C, and found that expression of the exonuclease deficient Polδ sensitizes cells to Ara-C. Furthermore, the exonuclease deficient Polδ reduced cell viability upon Ara-C to the same extent in both Polε exonuclease-proficient and -deficient cells, indicating that these two polymerases independently contribute to cellular tolerance to Ara-C. In contrast, wild-type, POLD1^exo−/+, and POLE1^exo−/− cells exhibited similar sensitivity to ddC, AZT, and alovudine, whilst POLD1^exo−/+/POLE1^exo−/− cells were considerably more sensitive compared with these cells, indicating that Polδ and Polε compensate for each other. Finally, we found that exonuclease activities of replicative polymerases cannot remove ACV from the end of nascent DNA. Taken together, our findings show that CTNAs have a differential impact on the replication fork, and the requirement of the exonuclease activities of replicative polymerases varies depending on the kinds of CTNAs.

链终止核苷类似物（ctna）在复制过程中被复制聚合酶delta （Polδ）和epsilon （Polε）整合到基因组中，并通过阻止随后的聚合抑制DNA合成。Polε的校对外切酶活性去除合并的CTNAs，从而有助于细胞对这些药物的耐受性。然而，Polδ对校对外切酶活性的贡献尚未明确，Polδ与Polε之间的关系也尚未得到很好的理解。我们在这里表明，Polδ的外切酶活性有助于细胞对CTNAs的耐受性，而Polδ和Polε外切酶的作用取决于CTNAs的种类。我们测试了POLD1exo−/+细胞对CTNA Ara-C的敏感性，发现外切酶缺陷Polδ的表达使细胞对Ara-C敏感。此外，在Polε外切酶精通和Polε外切酶缺乏的细胞中，同样程度地降低了细胞对Ara-C的生存能力，表明这两种聚合酶独立地促进了细胞对Ara-C的耐受。相比之下，野生型、POLD1exo−/+和POLE1exo−/−细胞对ddC、AZT和阿洛夫定的敏感性相似，而POLD1exo−/+/POLE1exo−/−细胞的敏感性明显高于这些细胞，表明Polδ和Polε相互补偿。最后，我们发现复制聚合酶的外切酶活性不能去除新生DNA末端的ACV。综上所述，我们的研究结果表明，CTNAs对复制叉有不同的影响，并且对复制聚合酶的外切酶活性的要求取决于CTNAs的种类。

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引用次数: 0

S-palmitoylation: An oily modification guardinggenome stability s -棕榈酰化：一种保护基因组稳定性的油性修饰

IF 2.7 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair

Pub Date : 2025-08-08 DOI: 10.1016/j.dnarep.2025.103883

Xiyuan Zheng , Xinying Wu , Lei Wang , Haohong Ouyang , Yeltokova Damira , Bin Peng , Xingzhi Xu

S-palmitoylation is a dynamic post-translational lipid modification that regulates key cellular processes. It is mediated by aspartate-histidine-histidine-cysteine-family palmitoyltransferases (PATs) and reversed by acyl-protein thioesterases (APTs). This modification influences protein stability, function, subcellular trafficking, and membrane interactions. Emerging evidence identifies protein palmitoylation as a key regulator of genomic stability and integrity: it modulates DNA repair pathways, replication fork dynamics, and stress response mechanisms. Consequently, dysregulated palmitoylation cycles can lead to an impaired replication stress response, and chromosomal instability, which might drive oncogenesis. In this review, we examine the critical roles of S-palmitoylation in maintaining genome stability and speculate on its therapeutic potential in counteracting malignancy-associated genomic instability.

s -棕榈酰化是一种动态的翻译后脂质修饰，调节关键的细胞过程。它由天冬氨酸-组氨酸-组氨酸-半胱氨酸家族棕榈酰基转移酶（PATs）介导，并由酰基蛋白硫酯酶（APTs）逆转。这种修饰影响蛋白质的稳定性、功能、亚细胞运输和膜相互作用。新出现的证据表明，蛋白棕榈酰化是基因组稳定性和完整性的关键调节器：它调节DNA修复途径、复制叉动力学和应激反应机制。因此，失调的棕榈酰化循环可导致复制应激反应受损和染色体不稳定，这可能会导致肿瘤发生。在这篇综述中，我们研究了s -棕榈酰化在维持基因组稳定性中的关键作用，并推测其在对抗恶性肿瘤相关基因组不稳定性方面的治疗潜力。

引用次数: 0

The model moss Physcomitrium patens relies heavily on homologous recombination to repair DNA double-strand breaks 模式苔藓壶状菌主要依靠同源重组修复DNA双链断裂

IF 2.7 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair

Pub Date : 2025-08-01 DOI: 10.1016/j.dnarep.2025.103881

Ayako N. Sakamoto , Yuichiro Yokota , Pierre-François Perroud , Yasuhiro Oshima , Fabien Nogué , Yoshihiro Hase

We previously showed that moss (Physcomitrium patens) cells are highly radioresistant and suggested that P. patens uses an efficient mechanism to repair DNA double-strand breaks (DSBs). Homologous recombination (HR), canonical non-homologous end-joining, and alternative end-joining are the major pathways used to repair DSBs. To identify the DSB repair pathway used in P. patens, we generated knockout (KO) plants for LIG4, POLQ, and RAD51B, which play major roles in canonical non-homologous end-joining, alternative end-joining, and HR, respectively. The KO plants were irradiated with γ-rays, and their radioresistance was evaluated. Although wild-type (WT), lig4, and polq plants showed comparable radioresistance, that of rad51b plants was drastically reduced. The radioresistance of rad51b polq plants was further reduced, whereas that of rad51b lig4 plants was similar to that of rad51b. Under γ-irradiation conditions at which the dry weight of the plants was reduced to 50 %, single base substitutions were predominantly induced in WT, lig4, and polq plants. In contrast, drastic sequence alterations, such as large deletions with or without insertions, chromosome inversions, or translocations, were induced in rad51b and rad51b polq plants. These results suggest that P. patens primarily uses the HR pathway for DSB repair, even in the presence of other pathways. Flow cytometry analysis of the WT and KO plants revealed that the majority of cells subjected to irradiation were in late S/G2 phase, suggesting that the sister chromatid served as a template for HR.

我们之前的研究表明，苔藓（Physcomitrium patens）细胞具有高度的抗辐射能力，并表明patens利用一种有效的机制来修复DNA双链断裂（DSBs）。同源重组（HR）、典型非同源末端连接和选择性末端连接是修复dsb的主要途径。为了确定植物中DSB的修复途径，我们构建了LIG4、POLQ和RAD51B的敲除（KO）植株，它们分别在典型的非同源末端连接、替代末端连接和HR中起主要作用。用γ射线照射KO植株，并对其辐射抗性进行评价。尽管野生型（WT）、lig4和polq植物表现出相当的辐射抗性，但rad51b植物的辐射抗性却急剧下降。rad51b polq植株的抗辐射能力进一步降低，而rad51b lig4植株的抗辐射能力与rad51b相似。在干重降低到50% %的γ辐照条件下，WT、lig4和polq植株主要发生单碱基取代。相比之下，在rad51b和rad51b polq植物中诱导了剧烈的序列改变，如插入或不插入的大缺失、染色体倒位或易位。这些结果表明，即使存在其他途径，P. patens也主要使用HR途径进行DSB修复。对WT和KO植株的流式细胞术分析显示，辐照后的大部分细胞处于S/G2期晚期，提示姐妹染色单体作为HR的模板。

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引用次数: 0

The role of DNA repair deficiency in lipid accumulation: A proof-of-concept study DNA修复缺陷在脂质积累中的作用：一项概念验证研究

IF 2.7 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair

Pub Date : 2025-08-01 DOI: 10.1016/j.dnarep.2025.103880

Houan Tu , Ibbo Willems , Anastasiya Mircheva , Victoria Claudino Bastos , Twan van den Beucken , Ludwig Dubois , Alexander H.V. Remels , Frederik-Jan van Schooten , Roger W.L. Godschalk , Sabine A.S. Langie

Animal models suggest an association between base excision repair (BER) deficiency and increased risk of obesity. To mechanistically investigate the effect of BER deficiency on intracellular lipid accumulation, we studied metabolic activity in in vitro BER knockdown (KD) models, targeting MutY DNA Glycosylase (MUTYH), Nth Like DNA Glycosylase 1 (NTHL1) and 8-Oxoguanine DNA Glycosylase (OGG1). We hypothesized that exposing BER deficient cells to lipids leads to reduced mitochondrial function and enhanced intracellular lipid accumulation. Stable BER KD models were generated in HepG2 cells using lentiviral shRNAs. KD was confirmed by qRT-PCR and BER activity was assessed using a modified comet assay. Upon exposure to a mixture of oleic and palmitic acid, DNA damage and mitochondrial copy number were only altered in NTHL1-KD cells, but all KD cells accumulated more intracellular lipids compared to lacZ control cells as determined by Oil-Red-O (ORO) staining. Compared to control cells, exposure to the fatty acid mixture increased proton leak in MUTYH-KD cells, indicating impaired mitochondrial function. Moreover, all KD cells showed reduced β-oxidation activity when exposed to the fatty acid mixture. Overall, this study shows that BER deficient HepG2 cells are more prone to accumulated lipids, which was associated with impaired mitochondrial function. These findings are relevant in understanding the underlying mechanisms that modulate the sensitivity of a person to accumulate lipids and increase their risk of developing metabolic diseases such as obesity and fatty liver disease.

动物模型表明，碱基切除修复（BER）缺陷与肥胖风险增加之间存在关联。为了研究BER缺乏对细胞内脂质积累的影响，我们在体外BER敲低（KD）模型中研究了代谢活性，目标是MutY DNA糖基化酶（MUTYH）、Nth样DNA糖基化酶1 （NTHL1）和8-氧鸟嘌呤DNA糖基化酶（OGG1）。我们假设将BER缺陷细胞暴露于脂质会导致线粒体功能降低和细胞内脂质积累增强。利用慢病毒shrna在HepG2细胞中生成稳定的BER KD模型。KD用qRT-PCR确认，BER活性用改良comet法测定。暴露于油酸和棕榈酸混合物后，DNA损伤和线粒体拷贝数仅在NTHL1-KD细胞中发生改变，但通过Oil-Red-O （ORO）染色发现，与lacZ对照细胞相比，所有KD细胞积累了更多的细胞内脂质。与对照细胞相比，暴露于脂肪酸混合物中MUTYH-KD细胞的质子泄漏增加，表明线粒体功能受损。此外，当暴露于脂肪酸混合物时，所有KD细胞都表现出β-氧化活性降低。总的来说，这项研究表明，BER缺陷的HepG2细胞更容易积累脂质，这与线粒体功能受损有关。这些发现与理解调节一个人积累脂质的敏感性和增加他们患代谢性疾病（如肥胖和脂肪肝疾病）风险的潜在机制有关。

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引用次数: 0

Cytosolic DNA and intracellular Ca2+: Maintaining genome stability during replication stress 胞质DNA和细胞内Ca2+：在复制胁迫下维持基因组的稳定性

IF 2.7 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair

Pub Date : 2025-08-01 DOI: 10.1016/j.dnarep.2025.103877

Shan Li , Hsiang-Ting Lu , Zhongsheng You

Maintaining genome stability during DNA replication is a critical cellular challenge. Various surveillance and repair mechanisms have evolved to cope with replication stress, which can be caused by environmental insults, metabolic byproducts, complex DNA structures in the genome, and replication-transcription conflicts. This perspective highlights a newly identified cytosolic DNA/Ca²⁺-dependent signaling pathway that plays a crucial role in protecting stalled replication forks. The pathway involves cytosolic DNA generation and its sensing by the cGAS-cGAMP-STING axis, TRPV2-mediated Ca²⁺ release from the ER, and activation of a CaMKK2-AMPK protein phosphorylation cascade that suppresses the EXO1 nuclease, thereby preventing aberrant fork processing and preserving chromosomal integrity. Separate from the ATR/Chk1 checkpoint, this cytoDNA/Ca²⁺-dependent pathway represents a non-redundant mechanism for genome maintenance, with potentially important implications for cancer formation and its treatment. Moreover, the intersection of this pathway with other signaling networks also enables coordinated regulation of genome maintenance, immune response, autophagy, and cellular senescence.

在DNA复制过程中保持基因组的稳定性是一个关键的细胞挑战。多种监视和修复机制已经发展到应对复制应激，这可能是由环境损害、代谢副产物、基因组中复杂的DNA结构和复制-转录冲突引起的。这一观点强调了新发现的细胞质DNA/Ca2+依赖信号通路，在保护停滞的复制分叉中起着至关重要的作用。该途径涉及胞质DNA的产生及其通过cGAS-cGAMP-STING轴的感知，trpv2介导的内质网Ca2+释放，以及抑制EXO1核酸酶的CaMKK2-AMPK蛋白磷酸化级联的激活，从而防止异常叉加工并保持染色体完整性。与ATR/Chk1检查点分离，这种细胞dna /Ca2+依赖途径代表了基因组维持的非冗余机制，对癌症的形成及其治疗具有潜在的重要意义。此外，该通路与其他信号网络的交叉也使基因组维持、免疫反应、自噬和细胞衰老的协调调节成为可能。

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引用次数: 0

DNA damage response of U2OS cells to low doses of gamma radiation delivered at very low dose rate U2OS细胞对低剂量极低剂量率γ辐射的DNA损伤反应

IF 2.7 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair

Pub Date : 2025-07-23 DOI: 10.1016/j.dnarep.2025.103875

Magdalena Płódowska , Wiktoria Krakowiak , Aneta Węgierek-Ciuk , Katarzyna Gałczyńska , Kinga Pasińska , Daniel Sobota , Paweł Wołowiec , Janusz Braziewicz , Anna Lankoff , Michał Arabski , Andrzej Wojcik , Halina Lisowska

The DNA damage response (DDR) of cells to low dose and low dose rate ionizing radiation is weak and remains a matter of controversy. The response can be studied by exposing cells to a low adapting dose (AD) and, subsequently to a high challenging dose (CD), where the response is strong. The aim of the present investigation was to analyse the DDR in cells exposed to very low dose rate AD and a high dose rate CD, with special focus on the role of the ATM kinase. U2OS cells (with wild type p53) were exposed to gamma radiation AD of 5.9 mGy at 31 µGy/h and of 10.5 mGy at 55 µGy/h. ATM was inhibited by addition of KU-55933. Adapted cells were exposed to a CD of 1 Gy photon radiation at 1 Gy/min. The studied endpoints included kinetics of 53BP1 foci formation and decay, cell cycle progression and gene expression. In some experiments, ATM was inhibited by KU-55933. AD alone led to a significant increase in 53BP1 foci, even in the presence of KU-55933, and it modulated the response to CD. KU-55933 failed to inhibit the induction of foci by AD and AD+CD, while foci induction by CD alone was inhibited. KU-55933 potentiated the G2 block in AD+CD-exposed cells. Gene expression was modulated by AD. In conclusion, AD differentially modulated the response of cells when given alone and after the CD, in absence and presence of KU-55933.

细胞对低剂量和低剂量率电离辐射的DNA损伤反应（DDR）较弱，目前仍存在争议。可以通过将细胞暴露于低适应剂量（AD）和随后的高挑战剂量（CD）来研究这种反应，其中反应很强。本研究的目的是分析暴露于极低剂量率AD和高剂量率CD的细胞中的DDR，特别关注ATM激酶的作用。U2OS细胞（野生型p53）分别暴露在31µGy/h 5.9 mGy和55µGy/h 10.5 mGy的伽马辐射下。KU-55933对ATM有抑制作用。适应后的细胞以1 Gy/min的速度暴露于1 Gy光子辐射的CD中。研究终点包括53BP1病灶形成和衰减动力学、细胞周期进展和基因表达。在一些实验中，KU-55933对ATM有抑制作用。即使在存在KU-55933的情况下，AD也能显著增加53BP1的病灶，并调节对CD的反应。KU-55933不能抑制AD和AD+CD对病灶的诱导，而单独CD对病灶的诱导则被抑制。KU-55933增强了AD+ cd暴露细胞的G2阻滞。AD可调节基因表达。总之，在KU-55933不存在和不存在的情况下，AD单独给药和CD后给药对细胞反应的调节是不同的。

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引用次数: 0

Using the safety scissors: DNA resection regulation at DNA double-strand breaks and telomeres 使用安全剪刀：DNA双链断裂和端粒的DNA切除调控

IF 3 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair

Pub Date : 2025-07-23 DOI: 10.1016/j.dnarep.2025.103876

Michael M. Soniat , Logan R. Myler

DNA resection is a universal process in genome maintenance by which one strand of DNA is degraded, leaving the other strand intact. This sometimes highly processive process is critical for many forms of DNA damage repair, replication-coupled repair, meiotic recombination, and telomere maintenance. Therefore, resection must be tightly regulated to prevent genome instability and promote faithful and accurate repair. Here, we review what is known about how resection functions and how it is controlled, using DNA double-strand break repair and telomere maintenance as examples. We address how resection is regulated in three independent steps: resection initiation, long-range processing, and termination. By addressing these mechanisms in the context of both pathways, we attempt to provide an overview of the similarities as well as the outstanding questions regarding how this robust process is regulated.

DNA切除是基因组维持中的一个普遍过程，其中一条DNA链被降解，留下另一条完整的DNA链。这种有时高度程序化的过程对于多种形式的DNA损伤修复、复制偶联修复、减数分裂重组和端粒维持至关重要。因此，切除必须严格控制，以防止基因组不稳定，促进忠实和准确的修复。本文以DNA双链断裂修复和端粒维护为例，回顾了目前已知的切除功能及其控制机制。我们在三个独立的步骤中解决了切除是如何调节的：切除起始，远程处理和终止。通过在这两种途径的背景下解决这些机制，我们试图提供相似之处的概述以及关于如何调节这一强大过程的突出问题。

引用次数: 0