Ubiquitination Governing DNA Repair - Implications in Health and Disease最新文献

{"title":"Maintenance of Genome Stability by Ubiquitination of DNA Repair Proteins in Mammalian Development and Disease","authors":"M. Shimada","doi":"10.5772/INTECHOPEN.79244","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.79244","url":null,"abstract":"To maintain genome DNA, DNA repair machinery has been developed in cellular life cycle. Multiple DNA repair pathways such as base excision repair, nucleotide excision repair, DNA cross link damage repair, DNA single strand break repair and DNA double strand break repair including nonhomologous end joining and homologous recombination are regulated by protein signal cascade. Because of limited gene number, protein posttranslational modification signal has advantage to control cell dynamics during development and senescence. This chapter focuses on how DNA repair proteins molecular modification including phosphorylation and ubiquitination contribute to genome stability pathway during mammalian development and disease.","PeriodicalId":344707,"journal":{"name":"Ubiquitination Governing DNA Repair - Implications in Health and Disease","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129417730","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}

{"title":"Review of the Ubiquitin Role in DNA Repair and Tumorigenesis, with Emphasis in Breast Cancer Treatment; Current Data and Future Options","authors":"Despoina Mourtzoukou, I. Drikos, N. Goutas, D. Vlachodimitropoulos","doi":"10.5772/INTECHOPEN.72600","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.72600","url":null,"abstract":"Breast carcinoma remains the commonest carcinoma among women worldwide. Despite the fact that impressive progression has been achieved so far regarding pathophysiol-ogy, histopathology and treatment of this cancer, there are still undiscovered fields on molecular and therapeutic levels. The need of resolving problems such as chemoresistance, recurrence and metastasis has led in revealing key molecules in the development and progression of malignancies, including breast tumors. In this review, we will briefly describe the functions of ubiquitin and post-translational modifications (PTMs) focusing specially in DNA repair and then discuss about the implication of ubiquitin and related molecules in tumorigenesis and specifically in breast carcinoma. So far there are only few drugs approved by FDA that target the ubiquitin system. There will be an analysis regarding the current and potential anti-cancer therapeutic strategies based on targeting specific ubiquitin-related molecules.","PeriodicalId":344707,"journal":{"name":"Ubiquitination Governing DNA Repair - Implications in Health and Disease","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133059002","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}

{"title":"Interlace between Chromatin Structure, DNA Repair and Ubiquitination","authors":"A. Bhatti, Shanzay Ahmed, Arooma Jannat, P. John","doi":"10.5772/INTECHOPEN.77175","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.77175","url":null,"abstract":"Chromatin remodeling, ubiquitylation, and DNA damage repair may be regarded as three discrete processes, but in fact, they are three extremely important interlinked processes that are imperative for the sustenance for life. Discrepancies in one will have outcomes that will affect the other processes direly. Exogenous and endogenous factors persistently affect the DNA by inducing damage and modifications. To sustain the integ - rity of life, these challenges need to be combated efficiently. For the preservation of the structural and functional components of the genome, nature has allowed them to evolve numerous pathways that constantly work to repair the induced damage. This sort of response is termed as DDR (DNA damage response) that include BER and NER (base excision and nucleotide excision repair, respectively) and non-homologous end joining and homologous recombination (NHEJ & HR). Since the DNA in cells is exceedingly organized and compressed, hence any process that utilizes DNA as its substrate requires essential remodeling of the chromatin structure. The chapter emphasizes on the phenom - enon of chromatin remodeling and ubiquitylation which subsequently affects the integral process of DNA damage repair.","PeriodicalId":344707,"journal":{"name":"Ubiquitination Governing DNA Repair - Implications in Health and Disease","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114566749","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}

{"title":"Ubiquitination and DNA Repair in Multiple Myeloma","authors":"L. Crawford, A. Irvine","doi":"10.5772/INTECHOPEN.70800","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.70800","url":null,"abstract":"Multiple myeloma (MM) is a hematological neoplasm characterized by the clonal pro- liferation of malignant plasma cells in the bone marrow. MM cells are characterized by genomic abnormalities that arise during the pathogenesis of disease and accumulate during progression. DNA repair pathways are critical to repair the plethora of DNA lesions that occur in MM, and deregulation of these pathways is implicated in disease onset and survival. The ubiquitin proteasome system has emerged as a central player in the regulation of DNA damage response (DDR). In this chapter, we review defects within the ubiquitin proteasome system that are associated with abnormal DNA damage response in MM and discuss current and potential novel ways of targeting these aberra- tions in the clinic.","PeriodicalId":344707,"journal":{"name":"Ubiquitination Governing DNA Repair - Implications in Health and Disease","volume":"117 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132904060","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}

{"title":"Ubiquitin and Fanconi Anemia","authors":"I. Drikos, A. Sachinidis","doi":"10.5772/INTECHOPEN.77123","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.77123","url":null,"abstract":"Fanconi anemia (FA) is an inherited disease distinct from the failure of bone marrow, growth disturbance, predisposition to cancer and concomitant chromosomal abnormalities. FA is associated with genes involved in DNA replication and DNA repair processes. More than 20 proteins have been identified to be related with FANC pathway opera tion. Necessary prerequisite for activation and regulation of FA pathway is the monou - biquitination of heterodimer FANCD2-FANCI by core proteins of Fanc complex. The monoubiquitination of FANCD2-FANCI is crucial for nuclear localization of heterodi - mer, binding to chromatin and regulation of DNA repair procedure. Mutations of genes of FANC complex proteins associated with deficiency of DNA repair pathways affected cellular and genome instability. The interaction between proteins and ubiquitination affected genomic integrity and stability.","PeriodicalId":344707,"journal":{"name":"Ubiquitination Governing DNA Repair - Implications in Health and Disease","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116999650","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}

{"title":"The Role of Deubiquitinases in DNA Double-Strand Break Repair","authors":"Jun Lu, Zhi-feng Xi, Xiao-Ying Huang, Q. Xia, Xi-Dai Long","doi":"10.5772/INTECHOPEN.73341","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.73341","url":null,"abstract":"DNA double-strand break (DSB) is a type of the most critical DNA lesions, and if not repaired promptly, it can result in cell death or a wide variety of genetic alterations including genome instability, large- or small-scale deletions, chromosome loss, loss of heterozygosity, and translocations. DSBs are repaired by double-strand break repair (DSBR), including nonhomologous end-joining (NHEJ) and homologous recombination (HR) pathway, and defects in these pathways cause genome instability and promote tumorigenesis. Accumulating evidence has demonstrated that the superfamily of deubiq- uitinases (DUBs) can regulate the action and stability of DNA repair enzymes involving in DSBR via modifying ubiquitination levels, a reversible posttranslational modification pathway. In this review, we will discuss ubiquitination/deubiquitination modification involving in DSBR genes, the role of DUBs in DSBR and corresponding mechanisms, and the potential effects of this modification on human diseases.","PeriodicalId":344707,"journal":{"name":"Ubiquitination Governing DNA Repair - Implications in Health and Disease","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129147784","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}

{"title":"Ubiquitylation and SUMOylation: An Orchestrated Regulation During DNA Damage Repair","authors":"Sara Espinoza-Corona, M. L. Bazán-Tejeda, Ulises Omar García Lepe, Rosa Ma. Bermúdez-Cruz","doi":"10.5772/INTECHOPEN.72583","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.72583","url":null,"abstract":"DNA double-strand breaks (DSBs) are cytotoxic DNA lesions that must be repaired as soon as possible because it can cause chromosomal aberrations and cell death. Homologous recombination (HR) and nonhomologous end joining (NHEJ) are the pathways that mainly repair these ruptures. HR process is finely regulated by synchronized posttranslational modifications including phosphorylation, ubiquitylation, and SUMOylation. The ubiquitin (Ub) modifications at damaged chromatin serve as recruitment platforms for DSB repair complexes by facilitating binding sites or regulating the interaction between proteins. Thus, SUMOylation has been associated with protein interaction, enzymatic activity, and chromatin mobility. Several DNA damage factors have been found to be ubiquitylated and SUMOylated including histones (H2AX) and proteins such as Mre11, Rad51, NBS1, and BRCA1. Regarding ubiquitylation-mediated regulation of DNA repair, RNF168 and RNF8 E3 ligases have turned out to be a key step in DNA damage repair regulation. Interestingly, there is evidence that the Ub signaling mechanism is ancestral, and this emphasizes its importance.","PeriodicalId":344707,"journal":{"name":"Ubiquitination Governing DNA Repair - Implications in Health and Disease","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121644755","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}

{"title":"The Roles of Cullin RING Ligases and the Anaphase Promoting Complex/Cyclosome in the Regulation of DNA Double Strand Break Repair","authors":"Debjani Pal, M. Summers","doi":"10.5772/INTECHOPEN.70482","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.70482","url":null,"abstract":"Historically, genome maintenance has been viewed as the largely independent activities of (1) ubiquitin ligases driving unidirectional cell cycle progression and, (2) the activity of cellular checkpoints that monitor DNA integrity and DNA replication. It is well established that the DNA damage response (DDR) checkpoint machinery promotes the activation of repair mechanisms in addition to opening a window for repair. Emerging evidence demonstrates an integrated network of the central cell cycle driving E3 ubiquitin ligases and the checkpoint machinery, as well as deubiquitinating enzymes, which intermittently cooperate and antagonize one another to define windows of checkpoint and repair activities to optimize genome stability and cellular health. A growing number of components of the ubiquitin machinery are involved in the DDR. Herein, we focus on the regulation of cell cycle checkpoints and the DNA repair mechanisms for double strand breaks (DSBs) by the coordinated activities of Cullin RING ligases (CRLs) and the anaphase promoting complex/cyclosome (APC/C). Cdh1 activity upon replication stress and during recovery from APC/C Cdh1 activation during the G2 DDR. In G2 APC/C Cdh1 targets Plk1 for degradation, while USP28 prevents it from targeting Claspin. USP28 also stabilizes 53BP1 after DNA damage as well, possibly from APC/C Cdh1 (represented by, “ ? ” ). Chk1 activation requires Claspin function, which is protected from SCF β TrCP -mediated degradation by USP29 and USP7. USP20 stabilizes both Claspin and Rad17 to promote Chk1 activity, possibly from APC/C Cdh1 ( “ ? ” ) as they are both substrates of the ligases. ATR and Chk1 prevent checkpoint recovery by inhibiting the Plk1 activators Aurora and Bora. Irreversible checkpoint activation is prevented by the degradation of active Chk1 by SCF Fbx6 . USP7 prevents the complete destabilization of Chk1. The inset shows a potential feedback loop between ATR-Chk1 and the Fanconi pathway. FANCM promotes Chk1 activation (indirectly via ATR). Chk1 promotes FANCM-promoted FANCD2 monoubiquitination. In turn, FANCD2-Ub promotes the CRL4 Cdt2 -mediated degradation of Chk1. USP1 deubiquitinates FANCD2, stabilizing Chk1. The negative feedback loop favors silencing of Chk1 due to the inactivation of USP1 upon DNA damage.","PeriodicalId":344707,"journal":{"name":"Ubiquitination Governing DNA Repair - Implications in Health and Disease","volume":"61 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114187560","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}

{"title":"The Five Families of DNA Repair Proteins and their Functionally Relevant Ubiquitination","authors":"Niko Moses, X. Zhang","doi":"10.5772/INTECHOPEN.71537","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.71537","url":null,"abstract":"The process of DNA repair, be it a response to replication dysfunction or genotoxic insult, is critical for the resolution of strand errors and the avoidance of DNA mismatches that could result in various molecular pathologies, including carcinogenic development. Here, we will describe the five main mechanisms by which DNA avoids mutation, namely the processes of base excision repair, mismatch repair, nucleotide excision repair, homologous recombination, and nonhomologous end joining. In particular, we will dis-sect the functional significance of various posttranslational modifications of the essential proteins within these pathways, including but not limited to ubiquitination, acetylation, and phosphorylation.","PeriodicalId":344707,"journal":{"name":"Ubiquitination Governing DNA Repair - Implications in Health and Disease","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131459663","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}

{"title":"The Cross Talk among Autophagy, Ubiquitination, and DNA Repair: An Overview","authors":"F. Nazio, Emiliano Maiani, F. Cecconi","doi":"10.5772/INTECHOPEN.71404","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.71404","url":null,"abstract":"Cellular plasticity is modulated by protein posttranslational modifications, which act on most intracellular pathways. Ubiquitination is a versatile posttranslational modifi cation (PTM) that influences protein fate, controlling their degradation or modulating their activity and subcellular localization. The ubiquitin proteasome system, UPS, and the autophagic pathway are the main degradative intracellular machineries, which rely on ubiquitination for their activation and/or the selective recycling of proteins and organ -elles. Recent findings indicate that the cross talk between UPS and autophagy plays a key role in controlling DNA repair pathways. Even being a cytoplasmic process, it is now clear that autophagy can directly impact on the correct activation of DNA repair. Of note, defects on autophagy are related to the impairment of homologous recombina tion repair and to an increase of the nonhomologous end joining repair activity. These evidences give new insights into the molecular processes underlying the DNA damage response and provide further explanation for the tumorigenesis associated with autoph - agy impairment. Moreover, these findings introduce new examples of synthetic lethality between autophagy and DNA repair genes and lead to the possible development of tar - get therapies for tumors with defective autophagy.","PeriodicalId":344707,"journal":{"name":"Ubiquitination Governing DNA Repair - Implications in Health and Disease","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129208697","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}