Ask about this productRelated genes to: RecQL5 Blocking Peptide
- Gene:
- RECQL5 NIH gene
- Name:
- RecQ like helicase 5
- Previous symbol:
- -
- Synonyms:
- RecQ5, FLJ90603
- Chromosome:
- 17q25
- Locus Type:
- gene with protein product
- Date approved:
- 1999-05-06
- Date modifiied:
- 2016-02-05
Related products to: RecQL5 Blocking Peptide
Related articles to: RecQL5 Blocking Peptide
- Transcription elongation by RNA polymerase II is a tightly regulated process that requires coordinated interactions between transcription elongation factors. IWS1 (Interacts with SPT6) has been implicated as a core elongation factor, but its molecular role remains unclear. We show that the intrinsically disordered C-terminal region of IWS1 contains short linear motifs (SLiMs) that multivalently engage the elongation machinery. Using cryo-electron microscopy, we map SLiMs in IWS1 that interact with Pol II subunits RPB1, RPB2, and RPB5, as well as elongation factors DSIF, SPT6, and ELOF1. Functional assays demonstrate that distinct IWS1 SLiMs specify IWS1 recruitment and IWS1-dependent transcription stimulation. IWS1 recruitment to the transcription elongation complex depends on association via the RPB1 jaw and binding of downstream DNA. Transcription elongation stimulation requires interactions with the RPB2 lobe and ELOF1. We identify other transcription elongation factors including ELOA and RECQL5 that bind the RPB1 jaw and demonstrate that IWS1 protects the activated transcription elongation complex from RECQL5 inhibition. We also reveal the binding of the histone reader and IWS1 interactor LEDGF to a transcribed downstream nucleosome. Our findings establish IWS1 as a modular scaffold that helps organize the transcription elongation complex, illustrating how disordered regions regulate transcription elongation. - Source: PubMed
Syau DellaSteinruecke FelixRoth SophieSchmid ErnstAdelman KarenWalter Johannes CFarnung Lucas - RECQL5 helicase has been implicated in the regulation of homologous recombination (HR), replication stress responses, transcription elongation, and resolution of transcription-replication conflicts. However, the underlying mechanism by which RECQL5 regulates multiple functions in genome maintenance is obscure. Here, we find that RECQL5 localizes to the stalled fork sites and restricts RAD51-mediated excessive fork reversal to promote unrestrained DNA synthesis. The replication defect in the absence of RECQL5 can be rescued by co-depletion of SMARCAL1/ZRANB3/HLTF/FBH1 fork remodelers and expression of HR-defective mutants of RAD51. The RAD51 regulation at the stalled fork sites by RECQL5 requires its binding to PCNA, RAD51, and helicase activity and is independent of its interaction with RNAPII. Notably, the RECQL5 mutant devoid of its interaction with RAD51 regulates transcription elongation comparable to that of wild-type RECQL5. Collectively, our data demonstrates that RECQL5 distinctly regulates transcription elongation and RAD51-mediated fork remodelling to safeguard the replicating genomes. - Source: PubMed
Nagraj TarunSahoo SatyaranjanKadupatil SharivaNagaraju Ganesh - Transcription elongation by RNA polymerase II is a tightly regulated process that requires coordinated interactions between elongation factors. IWS1 (Interacts with SPT6) has been implicated as a core elongation factor, but its molecular role remains unclear. We show that the intrinsically disordered C-terminal region of IWS1 contains short linear motifs (SLiMs) that multivalently engage the elongation machinery. Using cryo-electron microscopy, we map SLiMs in IWS1 that interact with Pol II subunits RPB1, RPB2, and RPB5, as well as elongation factors DSIF, SPT6, and ELOF1. Functional assays demonstrate that distinct IWS1 SLiMs specify IWS1 recruitment and IWS1-dependent transcription stimulation. IWS1 recruitment to the transcription elongation complex depends on association via the RPB1 jaw and binding of downstream DNA, and transcription elongation stimulation requires interactions with the RPB2 lobe and ELOF1. Based on these findings, we identify other transcription elongation factors including ELOA and RECQL5 that bind the RPB1 jaw and demonstrate that IWS1 protects the activated transcription elongation complex from RECQL5 inhibition. We also reveal the binding of the histone reader and IWS1 interactor LEDGF to a transcribed downstream nucleosome. Our findings establish IWS1 as a modular scaffold that organizes the transcription elongation complex, illustrating how disordered regions regulate transcription elongation. - Source: PubMed
Publication date: 2025/08/28
Syau DellaSteinruecke FelixRoth SophieSchmid ErnstAdelman KarenWalter JohannesFarnung Lucas - Complex chromosomal rearrangements (CCRs) present significant challenges and opportunities in cancer and congenital disease research. Reproducing these rearrangements experimentally in animal models has been challenging, limiting our insights into their mechanisms and impacts. Recql5 is a critical DNA helicase that participates in replication, transcription, and repair processes. We recently succeeded in facilitating CRISPR/Cas9-mediated induction of CCRs in mice, harboring Recql5 deletion. Some CCRs were accomplished by DNA repair mechanisms, including fork stalling and template switching (FoSTeS) and microhomology-mediated break-induced replication (MMBIR), characteristics reminiscent of chromoanasynthesis. This phenomenon is a part of chromoanagenesis, which includes other catastrophic chromosomal rearrangements. This chapter discusses the creation of CCR animal models, offering a new perspective for exploring the pathogenesis of chromosomal rearrangements. Recql5-mutant mice will prove to be a valuable tool for further genetic studies, potentially advancing our understanding of disease mechanisms and suggesting directions for future research. - Source: PubMed
Iwata SatoruIwamoto Takashi - RECQ5 is a member of the RECQ helicase family that maintains genomic stability. However, the molecular mechanism of RECQ5 in this biological process remains elusive. Here, we show that RECQ5 localizes in the dense fibrillar component of nucleolus and associates with several pre-rRNA processing factors. It recognizes pre-rRNA and is able to unwind double-stranded RNA in vitro. Loss of RECQ5 induces the accumulation of 47S, 30SL5', and 30S pre-rRNA, and the reduction of 21S pre-rRNA, suggesting that it regulates the processing of pre-rRNA. Cancer-associated mutations of RECQ5 abolish its nucleolar localization as well as its helicase activities. Moreover, lacking RECQ5 leads to the unprocessed pre-rRNA hybridizing with rDNA, triggering the R-loop formation and ATR activation. Since both RECQ5 and ATR protect genomic stability in nucleolus, suppression of RECQ5 sensitizes tumor cells to the ATR inhibitor treatment. Collectively, this study reveals that RECQ5 plays a crucial role in pre-rRNA processing and ribosomal DNA (rDNA) stability. - Source: PubMed
Ma YidiYu Xiaochun