DNA interstrand crosslinks (ICLs) are covalent bonds between opposing strands of the DNA helix which prevent DNA melting and subsequent DNA replication or RNA transcription. Here, we show that UV Stimulated Scaffold Protein A (UVSSA) participates in transcription-coupled repair of ICLs. UVSSA encodes a protein that regulates the activity of RNA polymerase II (Pol II) to facilitate the repair of UV lesions and to relieve transcription stress resulting from MYC activation. We show that UVSSA knockout sensitizes cells to ICL-inducing drugs, that UVSSA is specifically required for transcription-coupled repair of a single ICL in a fluorescence-based reporter assay, and that transcription-coupled repair of ICLs is defective in UVSSA−/−cells. UVSSA localizes to chromatin upon ICL damage, and interacts with transcribing Pol II, CSA, CSB, and TFIIH. The UVSSA-TFIIH interaction facilitates ICL repair. Finally, UVSSA expression positively correlates with ICL chemotherapy resistance in cancer cell lines. Our data strongly suggest that transcription-coupled ICL repair (TC-ICR) is abona fideICL repair mechanism that contributes to crosslinker drug resistance independently of replication-coupled ICL repair.GRAPHICAL ABSTRACTUVSSA facilitates transcription-coupled DNA interstrand crosslink repair by recruiting TFIIH to transcription machinery stalled at the lesion. Transcription-coupled ICL repair is required for survival following crosslink inducing drug exposure
Latin America and Asia have been tied for hundreds of years through a transcontinental trade network, which has culminated in their current economic interdependence. This interdependence necessitates cooperation, which can be bolstered through cultural understanding between the two continents. International student mobility is one way to foster intercultural relations, which are currently quite low between these regions. Canada has faced a similar struggle as Latin America to attract students in the Americas when faced with competition from US universities, but has had some successes which Latin American countries could learn from. This study therefore completes a scoping review of the literature to categorize barriers and enablers to academic mobility between higher education institutions (HEIs) in Asia, Canada, and Latin America and synthesizes relevant suggestions. An integrative literature search of qualitative and quantitative studies was conducted using six different databases. After considering inclusion and exclusion criteria, 33 studies were selected and analyzed. The results were categorized into six themes: Cultural, Academic and Professional, Linguistic, Economic, Program Structure, and Political Climate. Each theme included factors which enabled or hindered student mobility between Asia and the Americas. The findings highlight the need for Latinamerican HEIs to emphasize relevant initiatives and qualities that go beyond rankings, boost the use of English among academics and staff, actively reach out to Asian partners, and collaborate to develop credit transfer policies compatible with Asian institutions. These considerations could be all the more timely considering students are currently more open to virtual international opportunities in the midst of the COVID-19 pandemic, generating possibilities of greater collaboration between these regions of the world.
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