Preliminary study on the function of the POLD1 (CDC2) EXON2 c.56G>A mutation
Abstract Background Fanconi anemia (FA) is a rare recessive disease characterized by DNA damage repair deficiency, and DNA polymerase δ (whose catalytic subunit is encoded by POLD1, also known as CDC2) is closely related to DNA damage repair. Our previous study identified a novel POLD1 missense muta...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-08-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1280 |
| _version_ | 1797301043667664896 |
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| author | Jing Liu Yu Liu Jingxuan Fu Chengeng Liu Tingting Yang Xiaomin Zhang Min Cao Peichang Wang |
| author_facet | Jing Liu Yu Liu Jingxuan Fu Chengeng Liu Tingting Yang Xiaomin Zhang Min Cao Peichang Wang |
| author_sort | Jing Liu |
| collection | DOAJ |
| description | Abstract Background Fanconi anemia (FA) is a rare recessive disease characterized by DNA damage repair deficiency, and DNA polymerase δ (whose catalytic subunit is encoded by POLD1, also known as CDC2) is closely related to DNA damage repair. Our previous study identified a novel POLD1 missense mutation c.56G>A (p. Arg19>His) in FA family members. However, the function of the POLD1 missense mutation is currently unknown. This study aimed to uncover the biological function of the POLD1 missense mutation. Methods Stable cell lines overexpressing wild‐type POLD1 or mutant POLD1 (c.56G>A, p.Arg19His) were constructed by lentivirus infection. Cell growth curve analysis, cell cycle analysis, and a comet assay were used to analyze the function of the POLD1 mutation. Results The growth and proliferative ability of the cells with POLD1 mutation was decreased significantly compared with those of the wild‐type cells (Student's t test, p < .05). The percentage of cells in the G0/G1 phase increased, and the percentage of cells in the S phase decreased significantly when POLD1 was mutated (Student's t test, p < .05). Moreover, the Olive tail moment value of the cells with the POLD1 mutation was significantly higher than that of the cells with wild‐type POLD1 after H2O2 treatment. Conclusions The POLD1 mutation inhibited cell proliferation, slowed cell cycle progression, and reduced DNA damage repair. |
| first_indexed | 2024-03-07T23:15:45Z |
| format | Article |
| id | doaj.art-2b69c0c957ae41ca9724e18cf5450ff1 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:15:45Z |
| publishDate | 2020-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-2b69c0c957ae41ca9724e18cf5450ff12024-02-21T11:08:50ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-08-0188n/an/a10.1002/mgg3.1280Preliminary study on the function of the POLD1 (CDC2) EXON2 c.56G>A mutationJing Liu0Yu Liu1Jingxuan Fu2Chengeng Liu3Tingting Yang4Xiaomin Zhang5Min Cao6Peichang Wang7Department of Clinical Laboratory Xuanwu HospitalCapital Medical University Beijing People's Republic of ChinaDepartment of Clinical Laboratory Xuanwu HospitalCapital Medical University Beijing People's Republic of ChinaDepartment of Clinical Laboratory Xuanwu HospitalCapital Medical University Beijing People's Republic of ChinaDepartment of Clinical Laboratory Xuanwu HospitalCapital Medical University Beijing People's Republic of ChinaDepartment of Clinical Laboratory The Hospital of Shunyi District Beijing Beijing People's Republic of ChinaDepartment of Clinical Laboratory Xuanwu HospitalCapital Medical University Beijing People's Republic of ChinaDepartment of Clinical Laboratory Xuanwu HospitalCapital Medical University Beijing People's Republic of ChinaDepartment of Clinical Laboratory Xuanwu HospitalCapital Medical University Beijing People's Republic of ChinaAbstract Background Fanconi anemia (FA) is a rare recessive disease characterized by DNA damage repair deficiency, and DNA polymerase δ (whose catalytic subunit is encoded by POLD1, also known as CDC2) is closely related to DNA damage repair. Our previous study identified a novel POLD1 missense mutation c.56G>A (p. Arg19>His) in FA family members. However, the function of the POLD1 missense mutation is currently unknown. This study aimed to uncover the biological function of the POLD1 missense mutation. Methods Stable cell lines overexpressing wild‐type POLD1 or mutant POLD1 (c.56G>A, p.Arg19His) were constructed by lentivirus infection. Cell growth curve analysis, cell cycle analysis, and a comet assay were used to analyze the function of the POLD1 mutation. Results The growth and proliferative ability of the cells with POLD1 mutation was decreased significantly compared with those of the wild‐type cells (Student's t test, p < .05). The percentage of cells in the G0/G1 phase increased, and the percentage of cells in the S phase decreased significantly when POLD1 was mutated (Student's t test, p < .05). Moreover, the Olive tail moment value of the cells with the POLD1 mutation was significantly higher than that of the cells with wild‐type POLD1 after H2O2 treatment. Conclusions The POLD1 mutation inhibited cell proliferation, slowed cell cycle progression, and reduced DNA damage repair.https://doi.org/10.1002/mgg3.1280DNA polymerase δFanconi anemiaPOLD1 mutation |
| spellingShingle | Jing Liu Yu Liu Jingxuan Fu Chengeng Liu Tingting Yang Xiaomin Zhang Min Cao Peichang Wang Preliminary study on the function of the POLD1 (CDC2) EXON2 c.56G>A mutation Molecular Genetics & Genomic Medicine DNA polymerase δ Fanconi anemia POLD1 mutation |
| title | Preliminary study on the function of the POLD1 (CDC2) EXON2 c.56G>A mutation |
| title_full | Preliminary study on the function of the POLD1 (CDC2) EXON2 c.56G>A mutation |
| title_fullStr | Preliminary study on the function of the POLD1 (CDC2) EXON2 c.56G>A mutation |
| title_full_unstemmed | Preliminary study on the function of the POLD1 (CDC2) EXON2 c.56G>A mutation |
| title_short | Preliminary study on the function of the POLD1 (CDC2) EXON2 c.56G>A mutation |
| title_sort | preliminary study on the function of the pold1 cdc2 exon2 c 56g a mutation |
| topic | DNA polymerase δ Fanconi anemia POLD1 mutation |
| url | https://doi.org/10.1002/mgg3.1280 |
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