During its journey across a gene, RNA polymerase II has to contend with a number of obstacles to its progression, including nucleosomes, DNA-binding proteins, DNA damage, and sequences that are intrinsically difficult to transcribe. Not surprisingly, a large number of elongation factors have evolved to ensure that transcription stalling or arrest does not occur. If, however, the polymerase cannot be restarted, it becomes poly-ubiquitylated and degraded by the proteasome. This process is highly regulated, ensuring that only RNAPII molecules that cannot otherwise be salvaged are degraded. In this review, we describe the mechanisms and factors responsible for the last resort mechanism of transcriptional elongation. This article is part of a Special Issue entitled: RNA polymerase II Transcript Elongation.
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