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含有截短型DNA聚合酶β蛋白的PA1细胞对γ辐射更敏感。

PA1 cells containing a truncated DNA polymerase β protein are more sensitive to gamma radiation.

作者信息

Patra Anutosh, Nag Anish, Chakraborty Anindita, Bhattacharyya Nandan

机构信息

Department of Biotechnology, Panskura Banamali College, West Bengal, India.

Department of Life Sciences, CHRIST (Deemed to be University), Bangalore, India.

出版信息

Radiat Oncol J. 2022 Mar;40(1):66-78. doi: 10.3857/roj.2021.00689. Epub 2022 Mar 29.

DOI:10.3857/roj.2021.00689
PMID:35368202
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8984132/
Abstract

PURPOSE

DNA polymerase β (Polβ) acts in the base excision repair (BER) pathway. Mutations in DNA polymerase β (Polβ) are associated with different cancers. A variant of Polβ with a 97 amino acid deletion (PolβΔ), in heterozygous conditions with wild-type Polβ, was identified in sporadic ovarian tumor samples. This study aims to evaluate the gamma radiation sensitivity of PolβΔ for possible target therapy in ovarian cancer treatment.

MATERIALS AND METHODS

PolβΔ cDNA was cloned in a GFP vector and transfected in PA1 cells. Stable cells (PA1PolβΔ) were treated with 60Co sourced gamma-ray (0-15 Gy) to investigate their radiation sensitivity. The affinity of PolβΔ with DNA evaluated by DNA protein in silico docking experiments.

RESULTS

The result showed a statistically significant (p < 0.05) higher sensitivity towards radiation at different doses (0-15 Gy) and time-point (48-72 hours) for PA1PolβΔ cells in comparison with normal PA1 cells. Ten Gy of gamma radiation was found to be the optimal dose. Significantly more PA1PolβΔ cells were killed at this dose than PA1 cells after 48 hours of treatment via an apoptotic pathway. The in silico docking experiments revealed that PolβΔ has more substantial binding potential towards the dsDNA than wild-type Polβ, suggesting a possible failure of BER pathway that results in cell death.

CONCLUSION

Our study showed that the PA1PolβΔ cells were more susceptible than PA1 cells to gamma radiation. In the future, the potentiality of ionizing radiation to treat this type of cancer will be checked in animal models.

摘要

目的

DNA聚合酶β（Polβ）参与碱基切除修复（BER）途径。DNA聚合酶β（Polβ）的突变与不同癌症相关。在散发性卵巢肿瘤样本中鉴定出一种在杂合状态下与野生型Polβ存在97个氨基酸缺失的Polβ变体（PolβΔ）。本研究旨在评估PolβΔ对γ辐射的敏感性，以期为卵巢癌治疗提供可能的靶向治疗方法。

材料与方法

将PolβΔ cDNA克隆到绿色荧光蛋白（GFP）载体中，并转染到PA1细胞中。用60Co源的γ射线（0 - 15 Gy）处理稳定细胞（PA1PolβΔ），以研究其辐射敏感性。通过DNA与蛋白质的计算机对接实验评估PolβΔ与DNA的亲和力。

结果

结果显示，与正常PA1细胞相比，PA1PolβΔ细胞在不同剂量（0 - 15 Gy）和时间点（48 - 72小时）对辐射具有统计学上显著更高的敏感性（p < 0.05）。发现10 Gy的γ辐射为最佳剂量。在该剂量下处理48小时后，通过凋亡途径杀死的PA1PolβΔ细胞明显多于PA1细胞。计算机对接实验表明，PolβΔ对双链DNA（dsDNA）的结合潜力比野生型Polβ更大，这表明BER途径可能失效从而导致细胞死亡。

结论

我们的研究表明，PA1PolβΔ细胞比PA1细胞对γ辐射更敏感。未来，将在动物模型中检测电离辐射治疗这类癌症的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34bc/8984132/ce67341cf238/roj-2021-00689f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34bc/8984132/f38176895769/roj-2021-00689f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34bc/8984132/ac6162c6582a/roj-2021-00689f4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34bc/8984132/8bc811daeefe/roj-2021-00689f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34bc/8984132/c7c8c2fd9b7e/roj-2021-00689f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34bc/8984132/3d7bc9f56e97/roj-2021-00689f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34bc/8984132/ce67341cf238/roj-2021-00689f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34bc/8984132/f38176895769/roj-2021-00689f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34bc/8984132/a38592df65ba/roj-2021-00689f2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34bc/8984132/ac6162c6582a/roj-2021-00689f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34bc/8984132/36dad066666f/roj-2021-00689f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34bc/8984132/8bc811daeefe/roj-2021-00689f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34bc/8984132/c7c8c2fd9b7e/roj-2021-00689f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34bc/8984132/3d7bc9f56e97/roj-2021-00689f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34bc/8984132/ce67341cf238/roj-2021-00689f9.jpg

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本文引用的文献

1
ProMod3-A versatile homology modelling toolbox.ProMod3——一个通用的同源建模工具包。
PLoS Comput Biol. 2021 Jan 28;17(1):e1008667. doi: 10.1371/journal.pcbi.1008667. eCollection 2021 Jan.
2
Protein binding studies with human serum albumin, molecular docking and in vitro cytotoxicity studies using HeLa cervical carcinoma cells of Cu(ii)/Zn(ii) complexes containing a carbohydrazone ligand.含糖脒配体的 Cu(ii)/Zn(ii) 配合物与人血清白蛋白的蛋白结合研究、分子对接及 HeLa 宫颈癌细胞的体外细胞毒性研究。
Dalton Trans. 2020 Mar 3;49(9):2947-2965. doi: 10.1039/c9dt04656a.
3
Cancer statistics, 2020.
癌症统计数据，2020 年。
CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8.
4
Altering DNA Repair to Improve Radiation Therapy: Specific and Multiple Pathway Targeting.改变DNA修复以改善放射治疗：特异性和多途径靶向
Front Oncol. 2019 Oct 10;9:1009. doi: 10.3389/fonc.2019.01009. eCollection 2019.
5
Corilagin induces apoptosis, autophagy and ROS generation in gastric cancer cells in vitro.鞣花酸在体外诱导胃癌细胞凋亡、自噬和 ROS 的产生。
Int J Mol Med. 2019 Feb;43(2):967-979. doi: 10.3892/ijmm.2018.4031. Epub 2018 Dec 18.
6
Targeting BER enzymes in cancer therapy.针对癌症治疗中的 BER 酶。
DNA Repair (Amst). 2018 Nov;71:118-126. doi: 10.1016/j.dnarep.2018.08.015. Epub 2018 Aug 25.
7
DNA Repair Proteins as Therapeutic Targets in Ovarian Cancer.DNA修复蛋白作为卵巢癌的治疗靶点
Curr Protein Pept Sci. 2019;20(4):316-323. doi: 10.2174/1389203719666180914091537.
8
Radiation Treatment in Women with Ovarian Cancer: Past, Present, and Future.卵巢癌女性的放射治疗：过去、现在与未来
Front Oncol. 2017 Aug 21;7:177. doi: 10.3389/fonc.2017.00177. eCollection 2017.
9
BERing the burden of damage: Pathway crosstalk and posttranslational modification of base excision repair proteins regulate DNA damage management.承担损伤负担：碱基切除修复蛋白的信号通路串扰与翻译后修饰调控DNA损伤管理
DNA Repair (Amst). 2017 Aug;56:51-64. doi: 10.1016/j.dnarep.2017.06.007. Epub 2017 Jun 9.
10
HDOCK: a web server for protein-protein and protein-DNA/RNA docking based on a hybrid strategy.HDOCK：一个基于混合策略的蛋白质-蛋白质和蛋白质-DNA/RNA 对接的网络服务器。
Nucleic Acids Res. 2017 Jul 3;45(W1):W365-W373. doi: 10.1093/nar/gkx407.