RECQ5 helicase associates with the C-terminal repeat domain of RNA polymerase II during productive elongation phase of transcription.
It is known that transcription can induce DNA recombination, thus compromising genomic stability. RECQ5 DNA helicase promotes genomic stability by regulating homologous recombination. Recent studies have shown that RECQ5 forms a stable complex with RNA polymerase II (RNAPII) in human cells, but the cellular role of this association is not understood. Here, we provide evidence that RECQ5 specifically binds to the Ser2,5-phosphorylated C-terminal repeat domain (CTD) of the largest subunit of RNAPII, RPB1, by means of a Set2-Rpb1-interacting (SRI) motif located at the C-terminus of RECQ5. We also show that RECQ5 associates with RNAPII-transcribed genes in a manner dependent on the SRI motif. Notably, RECQ5 density on transcribed genes correlates with the density of Ser2-CTD phosphorylation, which is associated with the productive elongation phase of transcription. Furthermore, we show that RECQ5 negatively affects cell viability upon inhibition of spliceosome assembly, which can lead to the formation of mutagenic R-loop structures. These data indicate that RECQ5 binds to the elongating RNAPII complex and support the idea that RECQ5 plays a role in the maintenance of genomic stability during transcription.
Kanagaraj
Radhakrishnan
R
Institute of Molecular Cancer Research, University of Zurich, CH-8057 Zurich, Switzerland.
Huehn
Daniela
D
MacKellar
April
A
Menigatti
Mirco
M
Zheng
Lu
L
Urban
Vaclav
V
Shevelev
Igor
I
Greenleaf
Arno L
AL
Janscak
Pavel
P
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D002470:Cell Survival; D017124:Conserved Sequence; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism*; D053484:RecQ Helicases / Q000737:chemistry / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D017381:Spliceosomes / Q000378:metabolism; D014158:Transcription, Genetic
C506732:RECQL5 protein, human; D012319:RNA Polymerase II; D053484:RecQ Helicases