DNAPKcs-dependent arrest of RNA polymerase II transcription in the presence of DNA breaks

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)...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Pankotai Tibor
Bonhomme Céline
Chen David
Soutoglou Evi
Dokumentumtípus: Cikk
Megjelent: 2012-03
Sorozat:Nature structural & molecular biology 19 No. 3
Tárgyszavak:
doi:10.1038/nsmb.2224

mtmt:2537318
Online Access:http://publicatio.bibl.u-szeged.hu/5765
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520 3 |a 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. 
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