ISRN molecular biology最新文献

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Processing of damaged DNA ends for double-strand break repair in mammalian cells. 哺乳动物细胞双链断裂修复中受损DNA末端的加工。
ISRN molecular biology Pub Date : 2012-01-01 DOI: 10.5402/2012/345805
Lawrence F Povirk
{"title":"Processing of damaged DNA ends for double-strand break repair in mammalian cells.","authors":"Lawrence F Povirk","doi":"10.5402/2012/345805","DOIUrl":"10.5402/2012/345805","url":null,"abstract":"<p><p>Most DNA double-strand breaks (DSBs)formed in a natural environment have chemical modifications at or near the ends that preclude direct religation and require removal or other processing so that rejoining can proceed. Free radical-mediated DSBs typically bear unligatable 3'-phosphate or 3'-phosphoglycolate termini and often have oxidized bases and/or abasic sites near the break. Topoisomerase-mediated DSBs are blocked by covalently bound peptide fragments of the topoisomerase. Enzymes capable of resolving damaged ends include polynucleotide kinase/phosphatase, which restores missing 5'-phosphates and removes 3'-phosphates; tyrosyl-DNA phosphodiesterases I and II (TDP1 and TDP2), which remove peptide fragments of topoisomerases I and II, respectively, and the Artemis and Metnase endonucleases, which can trim damaged overhangs of diverse structure. TDP1 as well as APE1 can remove 3'-phosphoglycolates and other 3' blocks, while CtIP appears to provide an alternative pathway for topoisomerase II fragment removal. Ku, a core DSB joining protein, can cleave abasic sites near DNA ends. The downstream processes of patching and ligation are tolerant of residual damage, and can sometimes proceed without complete damage removal. Despite these redundant pathways for resolution, damaged ends appear to be a significant barrier to rejoining, and their resolution may be a rate-limiting step in repair of some DSBs..</p>","PeriodicalId":89785,"journal":{"name":"ISRN molecular biology","volume":"2012 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31867165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Tousled-Like Kinases as Guardians of Genome Integrity. 凌乱样激酶是基因组完整性的守护者。
ISRN molecular biology Pub Date : 2012-01-01 DOI: 10.5402/2012/627596
Arrigo De Benedetti
{"title":"The Tousled-Like Kinases as Guardians of Genome Integrity.","authors":"Arrigo De Benedetti","doi":"10.5402/2012/627596","DOIUrl":"10.5402/2012/627596","url":null,"abstract":"<p><p>The Tousled-like kinases (TLKs) function in processes of chromatin assembly, including replication, transcription, repair, and chromosome segregation. TLKs interact specifically (and phosphorylate) with the chromatin assembly factor Asf1, a histone H3-H4 chaperone, histone H3 itself at Ser10, and also Rad9, a key protein involved in DNA repair and cell cycle signaling following DNA damage. These interactions are believed to be responsible for the action of TLKs in double-stranded break repair and radioprotection and also in the propagation of the DNA damage response. Hence, I propose that TLKs play key roles in maintenance of genome integrity in many organisms of both kingdoms. In this paper, I highlight key issues of the known roles of these proteins, particularly in the context of DNA repair (IR and UV), their possible relevance to genome integrity and cancer development, and as possible targets for intervention in cancer management.</p>","PeriodicalId":89785,"journal":{"name":"ISRN molecular biology","volume":"2012 ","pages":"627596"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31592446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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