Abstract 1841: Characterizing long non-coding RNAs located within a replication origin at the human DBF4 locus.

Abstract Faithful replication of the entire genome only once per cell cycle is crucial to cell homeostasis. The importance of proper replication is manifested by the presence of a large library of strict regulatory mechanisms that a cell employs to govern entry into the cell cycle. Failure to regulate this “licensing” process may result in a state of aneuploidy which is a driving force in cancer development. Besides the licensing proteins, the precise mechanism of how a cell chooses or activates replication initiation points is still poorly understood in mammalian cells. We have been studying the replication origin located at the promoter region of the human DBF4 gene. This origin contains two replication initiation zones that fire in opposite directions sequentially in a time-dependant manner, which we've termed it asymmetrical bidirectional replication (ABR). We have recently discovered that the DBF4 origin region contains a unique distribution and modifications of histones, which appears to be relevant to the regulation of replication initiation. In addition, we also found high activities of long non-coding RNA (lncRNA) transcription up- and down-stream of the DBF4 origin. Our preliminary data suggest that the active transcription of the lncRNAs at this locus may have a regulatory function on the chromatin conformation, transcription and DNA replication. We are currently carrying out experiments to gain a better understanding of the mechanism how lncRNA transcription is regulated in the context of replication initiation and DBF4 transcription. Citation Format: Shawn Hughes, Kathleen Kylie, Julia Romero, Hoyun Lee. Characterizing long non-coding RNAs located within a replication origin at the human DBF4 locus. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1841. doi:10.1158/1538-7445.AM2013-1841