Direct inhibition of RNA polymerase II transcription by RECQL5. 2009

Ozan Aygün, and Xiaohua Xu, and Yilun Liu, and Hidehisa Takahashi, and Stephanie E Kong, and Ronald C Conaway, and Joan W Conaway, and Jesper Q Svejstrup
Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK, London Research Institute, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, United Kingdom.

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.

UI MeSH Term Description Entries
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012319 RNA Polymerase II A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure and transcribes DNA into RNA. It has different requirements for cations and salt than RNA polymerase I and is strongly inhibited by alpha-amanitin. EC 2.7.7.6. DNA-Dependent RNA Polymerase II,RNA Pol II,RNA Polymerase B,DNA Dependent RNA Polymerase II
D014158 Transcription, Genetic The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION. Genetic Transcription
D053484 RecQ Helicases A family of structurally-related DNA helicases that play an essential role in the maintenance of genome integrity. RecQ helicases were originally discovered in E COLI and are highly conserved across both prokaryotic and eukaryotic organisms. Genetic mutations that result in loss of RecQ helicase activity gives rise to disorders that are associated with CANCER predisposition and premature aging. RecQ Family of DNA Helicase,RecQ Helicase,ATP-Dependent DNA Helicase Q1,ATP-Dependent DNA Helicase Q4,ATP-Dependent DNA Helicase Q5,DNA Helicase Q1,DNA Helicase RecQL,DNA Helicase RecQL4,DNA Helicase, RecQ-like type 2,DNA-Dependent ATPase Q1,RECQL1 Helicase,RTS Helicase,RecQ Family of DNA Helicases,RecQ Protein,RecQ2 Helicase,RecQ3 Helicase,RecQ4 Helicase,RecQ5 Helicase,RecQ5L Helicase,RecQL Helicase,RecQL2 Helicase,RecQL3 Helicase,RecQL4 Helicase,ATP Dependent DNA Helicase Q1,ATP Dependent DNA Helicase Q4,ATP Dependent DNA Helicase Q5,DNA Dependent ATPase Q1,DNA Helicase, RecQ like type 2,Helicase, RECQL1,Helicase, RTS,Helicase, RecQ,Helicase, RecQ2,Helicase, RecQ3,Helicase, RecQ5,Helicase, RecQ5L,Helicase, RecQL,Helicase, RecQL2,Helicase, RecQL3,Helicase, RecQL4,Helicases, RecQ

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