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Genotoxic stress resulting from DNA damage is resolved through a signaling cascade known as the DNA Damage Response (DDR). The repair of damaged DNA is essential for cell survival, often requiring the DDR to attenuate other cellular processes such as the cell cycle, DNA replication, and transcription of genes not involved in DDR. The complex relationship between DDR and transcription has only recently been investigated. Transcription can facilitate the DDR in response to double-strand breaks (DSBs) and stimulate nucleotide excision repair (NER). However, transcription may need to be reduced to prevent potential interference with the repair machinery. In this review, we discuss various mechanisms that regulate transcription repression in response to different types of DNA damage, categorizing them by their range and duration of effect. Finally, we explore various models of transcription recovery following DNA damage-induced repression. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2008.02.040 Byline: Monika Gullerova (1), Nick J. Proudfoot (1) Keywords: RNA; CELLCYCLE; DNA Abstract: Transcription analyses reported in these studies reveal that convergent genes in S. pombe generate overlapping transcripts in the G1 phase of the cell cycle. We show that this double-strand (ds) RNA induces localized RNAi (Dicer and RITS) dependent transient heterochromatin structures including histone H3 lysine 9 trimethylation marks and Swi6 association. Consequently cohesin is recruited to these chromosomal positions through interaction with Swi6. In G2, localized cohesin is further concentrated into the intergenic regions of the convergent genes tested. This results in a block to further dsRNA formation by promoting gene-proximal transcription termination between the convergent genes. Cohesin release at mitosis leads to a new G1 phase with repeated dsRNA formation, transient heterochromatin, and cohesin recruitment. Our results uncover a hitherto unanticipated role for cohesin and further suggest a widespread role for the selective formation of dsRNA, heterochromatin, and subsequent cohesin recruitment in regulated transcriptional termination. Author Affiliation: (1) Sir William Dunn School of Pathology, University of Oxford, South Parks Rd, Oxford OX1 3RE, UK Article History: Received 3 July 2007; Revised 21 November 2007; Accepted 5 February 2008 Article Note: (miscellaneous) Published: March 20, 2008

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2007.11.003 Byline: Nick Proudfoot (1), Monika Gullerova (1) Abstract: There is extensive transcription throughout the eukaryotic genome resulting in both antisense transcripts from coding regions and cryptic unstable transcripts (CUTs) from intergenic regions. In this issue, demonstrate in the budding yeast that antisense transcripts, if stabilized by exosome impairment, are able to mediate gene silencing via the recruitment of histone deacetylases. Author Affiliation: (1) Sir William Dunn School of Pathology, South Parks Rd., OX1 3RE, University of Oxford, Oxford, UK

MicroRNAs (miRNAs) are small regulatory noncoding RNAs that are generated in the canonical RNA interference (RNAi) pathway. Drosha, DiGeorge syndrome critical region 8 (DGCR8) and Dicer are key players in miRNA biogenesis. Argonaute (Ago) proteins bind to miRNAs and are guided by them to find messenger RNA targets and carry out post‐transcriptional silencing of protein‐coding genes. Recently, emerging evidence suggests that RNAi factors have a range of noncanonical functions that are beyond miRNA biogenesis. These functions pertain to various biological processes, such as development, transcriptional regulation, RNA processing and maintenance of genome integrity. Here, we review recent literature reporting miRNA‐independent, noncanonical functions of Drosha, DGCR8, Dicer and Ago proteins and discuss the importance of these functions. [ABSTRACT FROM AUTHOR]