LEADER 01028nam0-2200349---450- 001 990009869870403321 005 20140707135455.0 010 $a978-88-6708-176-9 035 $a000986987 035 $aFED01000986987 035 $a(Aleph)000986987FED01 035 $a000986987 100 $a20140617d2013----km-y0itay50------ba 101 1 $aita 102 $aIT 105 $ay-------001yy 200 1 $aDistributismo$euna politica economica di equità e di equilibrio$fJohn C. Médaille$gprefazione di Bruno Amoroso 210 $aTorino$cLindau$d2013 215 $a343 p.$d21 cm 225 1 $a<>draghi 454 0$12001$aToward a truly free market$943502 610 0 $aPoltica economica$aSec. XX.-XXI 676 $a330$v21$zita 700 1$aMédaille,$bJohn C.$0523221 702 1$aAmoroso,$bBruno 801 0$aIT$bUNINA$gREICAT$2UNIMARC 901 $aBK 912 $a990009869870403321 952 $aVI C 1106$b51530$fFSPBC 959 $aFSPBC 996 $aToward a truly free market$943502 997 $aUNINA LEADER 04689nam 2200421z- 450 001 9910346749903321 005 20210212 035 $a(CKB)4920000000094215 035 $a(oapen)https://directory.doabooks.org/handle/20.500.12854/61459 035 $a(oapen)doab61459 035 $a(EXLCZ)994920000000094215 100 $a20202102d2018 |y 0 101 0 $aeng 135 $aurmn|---annan 181 $ctxt$2rdacontent 182 $cc$2rdamedia 183 $acr$2rdacarrier 200 00$aUbiquitin and Ubiquitin-Relative SUMO in DNA Damage Response 210 $cFrontiers Media SA$d2018 215 $a1 online resource (183 p.) 225 1 $aFrontiers Research Topics 311 08$a2-88945-441-X 330 $aDNA damage response (DDR) is a term that includes a variety of highly sophisticated mechanisms that cells have evolved in safeguarding the genome from the deleterious consequences of DNA damage. It is estimated that every single cell receives tens of thousands of DNA lesions per day. Failure of DDR to properly respond to DNA damage leads to stem cell dysfunction, accelerated ageing, various degenerative diseases or cancer. The sole function of DDR is to recognize diverse DNA lesions, signal their presence, activate cell cycle arrest and finally recruit specific DNA repair proteins to fix the DNA damage and thus prevent genomic instability. DDR is composed of hundreds of spatiotemporally regulated and interconnected proteins, which are able to promptly respond to various DNA lesions. So it is not surprising that mutations in genes encoding various DDR proteins cause embryonic lethality, malignancies, neurodegenerative diseases and premature ageing. The importance of DDR for cell survival and genome stability is unquestionable, but how the sophisticated network of hundreds of different DDR proteins is spatiotemporally coordinated is far from being understood. In the last ten years ubiquitin (ubiquitination) and the ubiquitin-relative SUMO (sumoylation) have emerged as essential posttranslational modifications that regulate DDR. Beside a plethora of ubiqutin and sumo E1-activating enzymes, E2-conjugating enzymes, E3-ligases and ubiquitin/sumo proteases involved in ubiquitination and sumoylation, the complexity of ubiqutin and sumo systems is additionally increased by the fact that both ubiquitin and sumo can form a variety of different chains on substrates which govern the substrate fate, such as its interaction with other proteins, changing its enzymatic activity or promoting substrate degradation. The importance of ubiquitin/SUMO systems in the orchestration of DDR is best illustrated in patients with mutations in E3-ubiquitin ligases BRCA1 or RNF168. BRCA1 is essential for proper function of DDR and its mutations lead to triple-negative breast and ovarian cancers. RNF168 is an E3 ubiquitin ligase, which creates the ubiquitin docking platform for recruitment of different DNA damage signalling and repair proteins at sites of DNA lesion, and its mutations cause RIDDLE syndrome characterized by radiosensitivity, immunodeficiency and learning disability. In addition, recently discovered the ubiquitin receptor protein SPRTN is part of the DNA replication machinery and its mutations cause early-onset hepatocellular carcinoma and premature ageing in humans. Despite more than 700 different enzymes directly involved in ubiquitination and sumoylation processes only few of them are known to play a role in DDR. Therefore, we feel that the role of ubiquitin and the ubiquitin-related SUMO in DDR is far from being understood, and that this is the emerging field that will hugely expand in the next decade due to the rapid development of a new generation of technologies, which will allow us a more robust and precise analyses of human genome, transcriptome and proteome. In this Research Topic we provide a comprehensive overview of our current understanding of ubiquitin and SUMO pathways in all aspects of DDR, from DNA replication to different DNA repair pathways, and demonstrate how alterations in these pathways cause genomic instability that is linked to degenerative diseases, cancer and pathological ageing. 606 $aGenetics (non-medical)$2bicssc 610 $aCancer 610 $aDNA damage response 610 $agenome stability 610 $aSUMO 610 $aSumoylation 610 $aUbiquitin 610 $aUbiquitination 615 7$aGenetics (non-medical) 700 $aKristijan Ramadan$4auth$01331087 702 $aIvan Dikic$4auth 906 $aBOOK 912 $a9910346749903321 996 $aUbiquitin and Ubiquitin-Relative SUMO in DNA Damage Response$93040115 997 $aUNINA