@article {Sridhara2017,
	title = {Transcription Dynamics Prevent RNA-Mediated Genomic Instability through SRPK2-Dependent DDX23 Phohsphorylation},
	journal = {Cell Reports},
	year = {2017},
	pages = {334{\textendash}343},
	abstract = {<p>Genomic instability is frequently caused by nucleic acid structures termed R-loops that are formed during transcription. Despite their harmful potential, mechanisms that sense, signal, and suppress these structures remain elusive. Here, we report that oscillations in transcription dynamics are a major sensor of R-loops. We show that pausing of RNA polymerase II (RNA Pol II) initiates a signaling cascade whereby the serine/arginine protein kinase 2 (SRPK2) phosphorylates the DDX23 helicase, culminating in the suppression of R-loops. We show that in the absence of either SRPK2 or DDX23, accumulation of R-loops leads to massive genomic instability revealed by high levels of DNA double-strand breaks (DSBs). Importantly, we found DDX23 mutations in several cancers and detected homozygous deletions of the entire DDX23 locus in 10 (17\%) adenoid cystic carcinoma (ACC) samples. Our results unravel molecular details of a link between transcription dynamics and RNA-mediated genomic instability that may play important roles in cancer development.</p>
},
	doi = {10.1016/j.celrep.2016.12.050},
	url = {https://doi.org/10.1016/j.celrep.2016.12.050},
	author = {Sridhara, Sreerama Chaitanya and Carvalho, Silvia and Ana Rita Grosso and Marcela, Lina and Carmo-fonseca, Maria and de Almeida, Sergio Fernandes}
}
