Albany 2013: Book of Abstracts
June 11-15 2013
©Adenine Press (2012)
Replication impairment as a source of transcription- and R-loop- associated recombination
Coordination of DNA replication with DNA-damage sensing, repair and cell cycle progression ensures with high probability genome integrity during cell divisions, thus preventing mutations and DNA rearrangements. Such events are usually associated with pathological disorders, including premature aging, various cancer predispositions and inherited diseases (Aguilera & Gómez-González, 2008). One important type of genome instability is that associated with transcription. Transcription of a DNA sequence increases its frequency of recombination, a phenomenon referred to as transcription-associated recombination (TAR). We will provide new data on the analysis of protein factors involved in transcription and RNA export that provide evidence that TAR is mediated by replication impairment and that it can be further enhanced by dysfunction of replication and repair factors in yeast and human cells via R-loops. Notably, our study provides a first connection between RNA processing, R-loops and chromatin structure that will be discussed. In addition, we have analyzed a number of mutants of the yeast RNA polymerase II that are dependent on double-strand repair functions for their viability. We show that in these mutants replication fork progression and DNA damage response are impaired by the presence of strong transcription-dependent obstacles. Our data provide evidence that specific alterations of mRNP biogenesis/export machinery lead to different ways by which chromatin structure and progression of replication can be compromised leading to genome instability.
This research has been supported by the Spanish Ministry of Economy and Innovation, Junta de Andalucía and the European Union (FEDER)
Aguilera, A., & Gómez-González, B. (2008). Genome instability: a mechanistic view of its causes and consequences. Nature Reviews Genetics 9, 204–217.
Department of Molecular Biology