The human DNA replication origin, located in the lamin B2 gene, interacts with the DNA topoisomerases I and II in a cell cycle-modulated manner. The topoisomerases interact in vivo and in vitro with precise bonds ahead of the start sites of bidirectional replication, within the prereplicative complex region; topoisomerase I is bound in M, early G1 and G1/S border and topoisomerase II in M and the middle of G1. The Orc2 protein competes for the same sites of the origin bound by either topoisomerase in different moments of the cell cycle; furthermore, it interacts on the DNA with topoisomerase II during the assembly of the pre-replicative complex and with DNA-bound topoisomerase I at the G1/S border. Inhibition of topoisomerase I activity abolishes origin firing. Thus, the two topoisomerases are closely associated with the replicative complexes, and DNA topology plays an essential functional role in origin activation.
In this conceptual article, our aim is to deconstruct the conceptualization of design framing and establish its essentially political nature. It demonstrates the positionality inherent within frames insofar as frames articulate subordinated or dominant status, or express normative understandings until challenged. In doing so, we build a conceptualization of the political foundations of design framing practices and their implications for those contexts within which design operates. Consequently, we argue for dissensual counter-framing design practices that unsettle institutionalized norms and ideologies played out within frames, and through which a form of political agency is sociomaterially enacted.
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