@article{4a28d20a17fc488a9c80687b6eb85f22,
title = "DNAPKcs-dependent arrest of RNA polymerase II transcription in the presence of DNA breaks",
abstract = "DNA double-strand break (DSB) repair interferes with ongoing cellular processes, including replication and transcription. Although the process of replication stalling upon collision of replication forks with damaged DNA has been extensively studied, the fate of elongating RNA polymerase II (RNAPII) that encounters a DSB is not well understood. We show that the occurrence of a single DSB at a human RNAPII-transcribed gene leads to inhibition of transcription elongation and reinitiation. Upon inhibition of DNA protein kinase (DNAPK), RNAPII bypasses the break and continues transcription elongation, suggesting that it is not the break per se that inhibits the processivity of RNAPII, but the activity of DNAPK. We also show that the mechanism of DNAPK-mediated transcription inhibition involves the proteasome-dependent pathway. The results point to the pivotal role of DNAPK activity in the eviction of RNAPII from DNA upon encountering a DNA lesion.",
author = "Tibor Pankotai and C{\'e}line Bonhomme and David Chen and Evi Soutoglou",
note = "Funding Information: We thank M. Kastan (St. Jude Children{\textquoteright}s Research Hospital) for the ER-I-PpoI plasmid. We are grateful to all the members of the Soutoglou laboratory as well as to K. Meaburn (National Cancer Institute, US National Institutes of Health (NCI-NIH)) and S. Biddie (Bristol Medical School) for constructive discussions and critical reading of the manuscript. We thank B. Reina (Institut de G{\'e}n{\'e}tique et de Biologie Mol{\'e}culaire et Cellulaire), I. Talianidis (Fleming Institute), B. Seraphin (Institut de G{\'e}n{\'e}tique et de Biologie Mol{\'e}culaire et Cellulaire), T. Misteli (NCI-NIH), and O. Shahar and M. Goldberg (Hebrew University) for comments on the manuscript. T.P. was supported by the Fondation pour la Recherche M{\'e}dicale en France (SPF20091217677), and research in Soutoglou{\textquoteright}s laboratory is funded by the Human Frontiers Science program (HFSP CDA), the Agence Nationale de la Recherche (ANR, programme Blanc), the Centre National de la Recherche Scientifique (CNRS, ATIP), the Institut National du Cancer (INCA libre) and the European FP7 framework (Marie Curie Reintegration grant). D.C. acknowledges the NIH (grants CA50519) and Cancer Research Institute of Texas (RP110465).",
year = "2012",
month = mar,
doi = "10.1038/nsmb.2224",
language = "English (US)",
volume = "19",
pages = "276--282",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "3",
}