DNA double-strand breaks induced by ionizing radiation are often accompanied by ancillary oxidative base damage that may prevent or delay their repair. In order to better define the features that make some DSBs repair-resistant, XLF-dependent nonhomologous end joining of blunt-ended DSB substrates having the oxidatively modified nonplanar base thymine glycol at the first (Tg1), second (Tg2), third (Tg3) or fifth (Tg5) positions from one 3′ terminus, was examined in human whole-cell extracts. Tg at the third position had little effect on end-joining even when present on both ends of the break. However, Tg as the terminal or penultimate base was a major barrier to end joining (>10-fold reduction in ligated products) and an absolute barrier when present at both ends. Dideoxy trapping of base excision repair intermediates indicated that Tg was excised from Tg1, Tg2 and Tg3 largely if not exclusively after DSB ligation. However, Tg was rapidly excised from the Tg5 substrate, resulting in a reduced level of DSB ligation, as well as slow concomitant resection of the opposite strand. Ligase reactions containing only purified Ku, XRCC4, ligase IV and XLF showed that ligation of Tg3 and Tg5 was efficient and only partially XLF-dependent, whereas ligation of Tg1 and Tg2 was inefficient and only detectable in the presence of XLF. Overall, the results suggest that promoting ligation of DSBs with proximal base damage may be an important function of XLF, but that Tg can still be a major impediment to repair, being relatively resistant to both trimming and ligation. Moreover, it appears that base excision repair of Tg can sometimes interfere with repair of DSBs that would otherwise be readily rejoined.

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The Covid-19 virus (CoV) has worsened due to its transmissibility worldwide. Several millions of people have been infected since 2019 when it was first detected. Unpredictable impact and disruption created by the pandemic influence global financial or economic crisis. This motivated governments to encourage more vaccination to manage the spread and counter the pandemic, thereby breaking the chain. However, despite the level of vaccination against CoV, that has not been found to prevent an individual from being infected. In addition, many transmission of SARS-CoV-2 occurs at the pre-symptomatic infection stage, which thus makes it difficult to contain. The impact of the vaccination and booster immunizations on viral load and transmissibility. There is a positive relationship where vaccination influences the transmission rate. This study aims to identify how critical the viral loads and asymptomatic virus status of the SARS-CoV-s influence the transmission of Omicron and how the quantitative SARS-CoV-s viral load assay corresponds to the clinical outcome while managing Covid-19 infected patients.

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Double-strand breaks (DSBs) induced by ionizing radiation are often accompanied by ancillary oxidative base damage that could prevent or delay their repair. In order to better define the features that make some DSBs repair-resistant, plasmid DSB substrates were constructed with two blunt ends, one having the oxidatively modified nonplanar base thymine glycol at the first, second or third positions from the 3′ terminus (Tg1, Tg2 and Tg3, respectively). End joining was examined in extracts of Bustel fibroblasts, wherein end joining is completely dependent on addition of exogenous recombinant XLF, and therefore reflects classical nonhomologous end joining. Tg at the third position had almost no effect on end-joining even when present on both ends of the break. However, the Tg1 and Tg2 substrates yielded tenfold to twentyfold less head-to-tail joins and no detectable head-to-head joins, suggesting that Tg as the terminal or penultimate base is a serious barrier to NHEJ and an absolute barrier when present at both ends. For all substrates, Tg-containing ligation products predominated at early times, and remarkably, a 3′ terminal Tg was in some cases directly ligated to an undamaged blunt end. Dideoxy trapping of base excision repair intermediates indicated that Tg was excised in the extracts, but largely if not exclusively after DSB ligation. For all substrates, accurate blunt end ligation without end trimming predominated. However addition of excess Artemis nuclease to the extracts resulted in a slightly shorter ligation product, and a slight increase in yield, for the Tg2 substrate only. For the Tg1 substrate, there was a distinct 2-hr delay between addition of substrate and the detection of ligated products, while the unmodified and Tg3 products showed a much shorter delay of ∼30 min. Overall, the results suggest that Tg can be a major impediment to DSB repair when present as the terminal or penultimate base, being relatively resistant to both trimming and ligation. Citation Format: Duaa Bafail, Sri Lakshmi Chalasani, Mohammed Al mohaini, Konstantin Akopiants, Lawrence F. Povirk. Tolerance and intolerance of proximal thymine glycol in DNA double-strand break repair by nonhomologous end joining. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3028. doi:10.1158/1538-7445.AM2015-3028