The Pol β variant containing exon α is deficient in DNA polymerase but has full dRP lyase activity

Dai, Da‐Peng; Prasad, Rajendra; Wilson, Samuel H.

doi:10.1038/s41598-019-45846-0

Cited by 3 publications

(2 citation statements)

References 47 publications

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“…1 DNA polymerase β (polb) is the smallest DNA polymerase in man and is the main DNA polymerase involved in the BER process, with dual-activities of DNA polymerization and dRP lyase. 2 During BER, DNA polymerase β can eliminate the dRP group and then fill the gap between the purine or pyrimidine sites that synthesize the injured DNA. In this process, abnormal expression or activity of polb will result in the accumulation of DNA lesions.…”

Section: Introductionmentioning

confidence: 99%

Polymorphic mutations in the polb gene promoter and their impact on transcriptional activity

Wang

et al. 2022

Thoracic Cancer

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Background: DNA polymerase β is one of the key enzymes involved in DNA damage repair and its proper expression is strictly controlled within different cells. We previously reported that three genetic mutations in the promoter region of the polb gene are prevalent in the Chinese Han population and two types of mutation are associated with thymic hyperplasia. The purpose of this study was to explore whether other mutated sites exist within the promoter region of the polb gene. Methods: Genomic DNAs of 421 healthy Chinese Han individuals were extracted from whole blood samples and used for gene amplification of the promoter region of the polb gene. After gel purification, PCR amplicons were sequenced by the Sanger sequencing method and used for sequence alignment with the Lasergene program. PCR products with novel mutations were then subcloned into luciferase reporter plasmid pGL4.10 and transfected into 293T cells for dual-luciferase activity analysis. Results: In total, 11 mutated sites were detected in the Chinese Han population and eight of these were reported for the first time. Using a dual luciferase reporter system, it was found that one novel mutation À142 C > G could decrease the transcription activity of the polb gene, whereas two novel mutations, À152_À151insC and À218 C > G, could significantly increase the transcription activity of the polb gene. Conclusions: High polymorphic sites could be found in the promoter region of polb gene and approximately half of them could influence its transcription activity.

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Section: Introductionmentioning

confidence: 99%

Polymorphic mutations in the polb gene promoter and their impact on transcriptional activity

Wang

et al. 2022

Thoracic Cancer

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“…DNA polymerase β is the smallest DNA polymerase in eukaryotic cells with a molecular weight of approximately 39 kDa. Its amino acid composition is highly conservative in the process of biological evolution and plays an important role in maintaining genetic stability 1–3 . The main function of DNA polymerase β is considered to be related to the process of DNA damage repair.…”

Section: Introductionmentioning

confidence: 99%

Two polymorphic mutations in promoter region of DNA polymerase β in relatively higher percentage of thymic hyperplasia patients

Zhou

Liu

et al. 2020

Thoracic Cancer

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Background DNA polymerase β is one of the key enzymes involved in the repair of DNA damage, and its high or low expression is closely related to tumorigenesis. In a previous study on lung cancer, we found three genetic mutations in the promoter region of the Polb gene could be detected in the Han Chinese population. The purpose of this study was to explore the relationship between these mutations and thymic hyperplasia. Methods Genomic DNA was extracted from 59 thymic hyperplasia patients by the salting out method and used for amplification of the promoter region of the Polb gene. The Polb gene mutation and its frequency were analyzed systematically by comparing them with the deposited wild‐type gene sequence in the NCBI database. The three typical mutated sequences in the promoter region of Polb gene, ‐196G > T, ‐168C > A and ‐188_‐187insCGCCC, were then amplified and ligated to pGL4.10 vector, so as to get the vectors used for the infection of 293T cells to explore their transcription activities by dual‐luciferase reporter system. Results Two types of mutations, ‐168C>A and‐188_‐187insCGCCC, were found in a significantly higher percentage in patients with thymic hyperplasia than in normal healthy people after sequencing analysis of 59 patients and 60 healthy controls. These results suggest that the two mutations may be closely related to thymic hyperplasia. in vitro functional experiments showed that‐168C>A could significantly increase promoter activity, whereas ‐188_‐187insCGCCC could significantly reduce promoter activity, suggesting that these two mutations may affect the expression level of the Polb gene in cells. Conclusions Two types of mutations in the promoter region of the Polb gene, ‐168C>A and‐188_‐187insCGCCC, are associated with thymic hyperplasia and may become a new risk factor for this disease. Key points Significant findings of the study Genetic mutations in the Polb gene are reported to be associated with different kinds of cancers. However, their relationship with thymic hyperplasia is still unclear. What this study adds For the first time, we report that two nucleotide mutations in the promoter region of the Polb gene are closely related with thymic hyperplasia after sequencing 59 patients and 60 healthy controls in the Han Chinese population.

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A duplexed high-throughput mass spectrometry assay for bifunctional POLB polymerase and lyase activity

Gurard-Levin,

McMillan,

Whittington

et al. 2024

SLAS Technology

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The Pol β variant containing exon α is deficient in DNA polymerase but has full dRP lyase activity

Cited by 3 publications

References 47 publications

Polymorphic mutations in the polb gene promoter and their impact on transcriptional activity

Polymorphic mutations in the polb gene promoter and their impact on transcriptional activity

Two polymorphic mutations in promoter region of DNA polymerase β in relatively higher percentage of thymic hyperplasia patients

A duplexed high-throughput mass spectrometry assay for bifunctional POLB polymerase and lyase activity

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