caa a22 4500 606175237 CHVBK 20210128100742.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s00018-014-1820-z doi (NATIONALLICENCE)springer-10.1007/s00018-014-1820-z New paradigms in the repair of oxidative damage in human genome: mechanisms ensuring repair of mutagenic base lesions during replication and involvement of accessory proteins [Elektronische Daten] [Arijit Dutta, Chunying Yang, Shiladitya Sengupta, Sankar Mitra, Muralidhar Hegde] Oxidized bases in the mammalian genome, which are invariably mutagenic due to their mispairing property, are continuously induced by endogenous reactive oxygen species and more abundantly after oxidative stress. Unlike bulky base adducts induced by UV and other environmental mutagens in the genome that block replicative DNA polymerases, oxidatively damaged bases such as 5-hydroxyuracil, produced by oxidative deamination of cytosine in the template strand, do not block replicative polymerases and thus need to be repaired prior to replication to prevent mutation. Following up our earlier studies, which showed that the Nei endonuclease VIII like 1 (NEIL1) DNA glycosylase, one of the five base excision repair (BER)-initiating enzymes in mammalian cells, has enhanced expression during the S-phase and higher affinity for replication fork-mimicking single-stranded (ss) DNA substrates, we recently provided direct experimental evidence for NEIL1's role in replicating template strand repair. The key requirement for this event, which we named as the ‘cow-catcher' mechanism of pre-replicative BER, is NEIL1's non-productive binding (substrate binding without product formation) to the lesion base in ss DNA template to stall DNA synthesis, causing fork regression. Repair of the lesion in reannealed duplex is then carried out by NEIL1 in association with the DNA replication proteins. NEIL1 (and other BER-initiating enzymes) also interact with several accessory and non-canonical proteins including the heterogeneous nuclear ribonucleoprotein U and Y-box-binding protein 1 as well as high mobility group box 1 protein, whose precise roles in BER are still obscure. In this review, we have discussed the recent advances in our understanding of oxidative genome damage repair pathways with particular focus on the pre-replicative template strand repair and the role of scaffold factors like X-ray repairs cross-complementing protein 1 and poly (ADP-ribose) polymerase 1 and other accessory proteins guiding distinct BER sub-pathways. Springer Basel, 2015 Base excision repair nationallicence Single strand break repair nationallicence DNA glycosylase nationallicence Reactive oxygen species nationallicence Oxidized DNA bases nationallicence Pre-replicative repair of oxidized bases nationallicence NEIL1 nationallicence Non-canonical proteins nationallicence Dutta Arijit Department of Radiation Oncology, Houston Methodist Research Institute, 77030, Houston, TX, USA aut Yang Chunying Department of Radiation Oncology, Houston Methodist Research Institute, 77030, Houston, TX, USA aut Sengupta Shiladitya Department of Radiation Oncology, Houston Methodist Research Institute, 77030, Houston, TX, USA aut Mitra Sankar Department of Radiation Oncology, Houston Methodist Research Institute, 77030, Houston, TX, USA aut Hegde Muralidhar Department of Radiation Oncology, Houston Methodist Research Institute, 77030, Houston, TX, USA aut Cellular and Molecular Life Sciences Springer Basel 72/9(2015-05-01), 1679-1698 1420-682X 72:9<1679 2015 72 18 https://doi.org/10.1007/s00018-014-1820-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-014-1820-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Dutta Arijit Department of Radiation Oncology, Houston Methodist Research Institute, 77030, Houston, TX, USA aut NATIONALLICENCE 700 1- Yang Chunying Department of Radiation Oncology, Houston Methodist Research Institute, 77030, Houston, TX, USA aut NATIONALLICENCE 700 1- Sengupta Shiladitya Department of Radiation Oncology, Houston Methodist Research Institute, 77030, Houston, TX, USA aut NATIONALLICENCE 700 1- Mitra Sankar Department of Radiation Oncology, Houston Methodist Research Institute, 77030, Houston, TX, USA aut NATIONALLICENCE 700 1- Hegde Muralidhar Department of Radiation Oncology, Houston Methodist Research Institute, 77030, Houston, TX, USA aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/9(2015-05-01), 1679-1698 1420-682X 72:9<1679 2015 72 18