DNA repair最新文献

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DLG2 impairs dsDNA break repair and maintains genome integrity in neuroblastoma. DLG2在神经母细胞瘤中损害dsDNA断裂修复并维持基因组完整性。

DNA repair Pub Date : 2021-05-05 DOI: 10.21203/RS.3.RS-495251/V1

Simon Keane, H. de Weerd, K. Ejeskär

{"title":"DLG2 impairs dsDNA break repair and maintains genome integrity in neuroblastoma.","authors":"Simon Keane, H. de Weerd, K. Ejeskär","doi":"10.21203/RS.3.RS-495251/V1","DOIUrl":"https://doi.org/10.21203/RS.3.RS-495251/V1","url":null,"abstract":"BACKGROUND\u0000In primary neuroblastoma, deletions on chromosome 11q are known to result in an increase in the total number of chromosomal breaks. The DNA double-strand break repair pathways mediated by NHEJ are often upregulated in cancer. DLG2, a candidate tumor suppressor gene on chromosome 11q, has previously been implicated in DNA repair.\u0000\u0000\u0000METHODS\u0000We evaluated an association between gene expression and neuroblastoma patient outcome, risk categorization, and 11q status using publicly available microarray data from independent neuroblastoma patient datasets. Functional studies were conducted using comet assay and H2AX phosphorylation in neuroblastoma cell lines and in the fruit fly with UVC-induced DNA breaks.\u0000\u0000\u0000RESULTS\u0000We show that the NHEJ genes PARP1 and FEN1 are over expressed in neuroblastoma and restoration of DLG2 impairs their gene and protein expression. When exposed to UVC radiation, cells with DLG2 over expression show less DNA fragmentation and induce apoptosis in a p53 S46 dependent manner. We could also confirm that DLG2 over expression results in CHK1 phosphorylation consistent with previous reports of G2/M maintenance.\u0000\u0000\u0000CONCLUSIONS\u0000Taken together, we show that DLG2 over expression increases p53 mediated apoptosis in response to etoposide and UVC mediated genotoxicity and reduced DNA replication machinery.","PeriodicalId":93982,"journal":{"name":"DNA repair","volume":"112 1","pages":"103302"},"PeriodicalIF":0.0,"publicationDate":"2021-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47504505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Bacillus Fragment DNA polymerase mutant I716M 芽孢杆菌片段DNA聚合酶突变体I716M

DNA repair Pub Date : 2020-03-25 DOI: 10.2210/pdb6p5c/pdb

M. L. Hamm, Anarosa A. Garcia, Rachel Gilbert, Manavi Johri, M. Ricart, Samantha L. Sholes, Laura A. Murray-Nerger, Eugene Wu

{"title":"Bacillus Fragment DNA polymerase mutant I716M","authors":"M. L. Hamm, Anarosa A. Garcia, Rachel Gilbert, Manavi Johri, M. Ricart, Samantha L. Sholes, Laura A. Murray-Nerger, Eugene Wu","doi":"10.2210/pdb6p5c/pdb","DOIUrl":"https://doi.org/10.2210/pdb6p5c/pdb","url":null,"abstract":"Abstract 8-oxo-2′-deoxyguanosine (OdG) is a prominent DNA lesion that can direct the incorporation of dCTP or dATP during replication. As the latter reaction can lead to mutation, the ratio of dCTP/dATP incorporation can significantly affect the mutagenic potential of OdG. Previous work with the A-family polymerase BF and seven analogues of OdG identified a major groove amino acid, Ile716, which likely influences the dCTP/dATP incorporation ratio opposite OdG. To further probe the importance of this amino acid, dCTP and dATP incorporations opposite the same seven analogues were tested with two BF mutants, I716M and I716A. Results from these studies support the presence of clashing interactions between Ile716 and the C8-oxygen and C2-amine during dCTP and dATP incorporations, respectively. Crystallographic analysis suggests that residue 716 alters the conformation of the template base prior to insertion into the active site, thereby affecting enzymatic efficiency. These results are also consistent with previous work with A-family polymerases, which indicate they have tight, rigid active sites that are sensitive to template perturbations.","PeriodicalId":93982,"journal":{"name":"DNA repair","volume":"89 1","pages":"102826-102826"},"PeriodicalIF":0.0,"publicationDate":"2020-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43135037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Importance of homo-dimerization of Fanconi-associated nuclease 1 in DNA flap cleavage Fanconi相关核酸酶1同源二聚体在DNA瓣切割中的重要性

DNA repair Pub Date : 2017-12-18 DOI: 10.1101/236208

T. Rao, S. Longerich, Weixing Zhao, H. Aihara, P. Sung, Y. Xiong

引用次数: 6

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