Direct inhibition of RNA polymerase II transcription by RECQL5.
DNA helicases of the RECQ family are important for maintaining genome integrity, from bacteria to humans. Although progress has been made in understanding the biochemical role of some human RECQ helicases, that of RECQL5 remains elusive. We recently reported that RECQL5 interacts with RNA polymerase II (RNAPII), pointing to a role for the protein in transcription. Here, we show that RECQL5 inhibits both initiation and elongation in transcription assays reconstituted with highly purified general transcription factors and RNAPII. Such inhibition is not observed with the related, much more active RECQL1 helicase or with a version of RECQL5 that has normal helicase activity but is impaired in its ability to interact with RNAPII. Indeed, RECQL5 helicase activity is not required for inhibition. We discuss our findings in light of the fact that RECQ5(-/-) mice have elevated levels of DNA recombination and a higher incidence of cancer.
Aygün
Ozan
O
Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK, London Research Institute, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, United Kingdom.
Xu
Xiaohua
X
Liu
Yilun
Y
Takahashi
Hidehisa
H
Kong
Stephanie E
SE
Conaway
Ronald C
RC
Conaway
Joan W
JW
Svejstrup
Jesper Q
JQ
D002460:Cell Line; D006801:Humans; D011485:Protein Binding; D012319:RNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
C506732:RECQL5 protein, human; D012319:RNA Polymerase II; D053484:RecQ Helicases