Paf1 and Ctr9 subcomplex formation is essential for Paf1 complex assembly and functional regulation

Xie, Ying; Zheng, Minying; Chu, Xinlei; Chen, Yue; Xu, Honglei; Wang, Jiawei; Zhou, Hao; Long, Jiafu

doi:10.1038/s41467-018-06237-7

Cited by 36 publications

(32 citation statements)

References 70 publications

(91 reference statements)

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“…However, in higher organisms, including Drosophila , the dependence of PAF1C on DSIF for recruitment to elongating RNAPII is less clear. Rtf1 is less tightly associated with other PAF1C components while recent work shows that PAF1C recruitment can be DSIF-independent in mammals 42–46 . Further, Leo1 of PAF1C directly interacts with elongating RNAPII 37 and the C9orf72 gene ( see Fig.…”

Section: Discussionmentioning

confidence: 96%

Toxic expanded GGGGCC repeat transcription is mediated by the PAF1 complex in C9orf72-associated FTD

et al. 2019

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An expanded (G4C2)30+ repeat within C9orf72 is the most prominent mutation in familial FTD and ALS. Through an unbiased, large-scale screen in (G4C2)49-expressing Drosophila we identify the CDC73/PAF1 complex (PAF1C), a transcriptional regulator of RNAPII, as a suppressor of G4C2-associated toxicity. Depletion of PAF1C reduces RNA and GR-dipeptide production from (G4C2)30+ transgenes. Interestingly, dPAF1C components, dPaf1 and dLeo1 appear selective for transcription of long, toxic repeat expansions, but not shorter, non-toxic expansions. In yeast, scPAF1C components regulate expression of both sense and anti-sense repeats. PAF1C is upregulated upon expression of (G4C2)30+ in flies and mice. hPaf1 is also upregulated in C9+ -derived cells and its heterodimer partner, hLeo1, binds C9 + repeat chromatin. In C9+ FTD, hPAF1 and hLEO1 are upregulated and their expression positively correlates with expression of repeat-containing C9orf72 transcripts. These data indicate that PAF1C activity is an important factor for transcription of the long, toxic repeat in C9+ FTD.

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Section: Discussionmentioning

confidence: 96%

Toxic expanded GGGGCC repeat transcription is mediated by the PAF1 complex in C9orf72-associated FTD

et al. 2019

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“…Similarly, the involvement of Wdr61 in CSR was also excluded, as all of the mutants regardless of their CSR complementation efficiency showed a similar level of interaction with this protein (Fig 7C). In addition, we did not detect Ctr9, a key component of the Paf1 complex (Xie et al, 2018), in our Phf5a co-IPed proteins (Appendix Table S1). Therefore, the possible involvement of Wdr61 or Ctr9 (Paf1/ski8 complex) in Phf5a-associated CSR was nullified.…”

Section: Phf5a Forms a Chromatin Complex With P400 And Sf3b Componentsmentioning

confidence: 79%

Phf5a regulates DNA repair in class switch recombination via p400 and histone H2A variant deposition

et al. 2021

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Antibody class switch recombination (CSR) is a locus-specific genomic rearrangement mediated by switch (S) region transcription, activation-induced cytidine deaminase (AID)-induced DNA breaks, and their resolution by non-homologous end joining (NHEJ)-mediated DNA repair. Due to the complex nature of the recombination process, numerous cofactors are intimately involved, making it important to identify rate-limiting factors that impact on DNA breaking and/or repair. Using an siRNA-based loss-of-function screen of genes predicted to encode PHD zinc-finger-motif proteins, we identify the splicing factor Phf5a/Sf3b14b as a novel modulator of the DNA repair step of CSR. Loss of Phf5a severely impairs AID-induced recombination, but does not perturb DNA breaks and somatic hypermutation. Phf5a regulates NHEJ-dependent DNA repair by preserving chromatin integrity to elicit optimal DNA damage response and subsequent recruitment of NHEJ factors at the S region. Phf5a stabilizes the p400 histone chaperone complex at the locus, which in turn promotes deposition of H2A variant such as H2AX and H2A.Z that are critical for the early DNA damage response and NHEJ, respectively. Depletion of Phf5a or p400 blocks the repair of both AID-and I-SceI-induced DNA double-strand breaks, supporting an important contribution of this axis to programmed as well as aberrant recombination.

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“…Decoration of cancer cell membrane protein to the nanoparticle shell has been shown to improve the biological property of the nanoparticle, especially the homotypic recognition ability 29 , 39 . In this regard, western blotting experiments were next carried out to confirm the existence of membrane proteins by using four cell membrane adherence molecular related antibodies, including EpCAM, N-cadherin, Na + /K + -ATPase and CD44 28 , 40 , 41 . As depicted in Figure 2 A, 4T1 cells lysate (Ⅰ), cell membrane fragments (Ⅱ) as well as CM-GMNPs (Ⅲ) exhibit similar protein bands, implying that the membrane proteins are successfully transferred to CM-GMNPs.…”

Section: Resultsmentioning

confidence: 99%

Cell membrane coated smart two-dimensional supraparticle for in vivo homotypic cancer targeting and enhanced combinational theranostics

Zhang¹,

Ye²,

Liu³

et al. 2021

Nanotheranostics

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Development of intelligent and multifunctional nanoparticle for the diagnosis and treatment of cancer has drawn great attention recently. In this work, we design a smart two-dimensional (2D) supraparticle for tumor targeted magnetic resonance imaging (MRI)/photothermal imaging (PTI) and chemo/photothermal therapy (PTT). Methods: The nanoparticle consists of a manganese dioxide (MnO 2 ) nanosheet coated gold nanorod (GNR) core (loading with chemotherapeutics doxorubicin (DOX)), and cancer cell membrane shell (denoted as CM-DOX-GMNPs). Decoration of cell membrane endows the nanoparticle with greatly improved colloidal stability and homotypic cancer cell targeting ability. Once the nanoparticles enter tumor cells, MnO 2 nanosheets can be etched to Mn 2+ by glutathione (GSH) and acidic hydrogen peroxide (H 2 O 2 ) in the cytosol, leading to the release of DOX. Meanwhile, stimuli dependent releasing of Mn 2+ can act as MRI contrast agent for tumor diagnosis. Illumination with near-infrared (NIR) light, photothermal conversion effect of GNRs can be activated for synergistic cancer therapy. Results: In vivo results illustrate that the CM-DOX-GMNPs display tumor specific MRI/PTI ability and excellent inhibition effect on tumor growth. Conclusion: This bioinspired nanoparticle presents an effective and intelligent approach for tumor imaging and therapy, affording valuable guidance for the rational design of robust theranostics nanoplatform.

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Paf1 and Ctr9 subcomplex formation is essential for Paf1 complex assembly and functional regulation

Cited by 36 publications

References 70 publications

Toxic expanded GGGGCC repeat transcription is mediated by the PAF1 complex in C9orf72-associated FTD

Toxic expanded GGGGCC repeat transcription is mediated by the PAF1 complex in C9orf72-associated FTD

Phf5a regulates DNA repair in class switch recombination via p400 and histone H2A variant deposition

Cell membrane coated smart two-dimensional supraparticle for in vivo homotypic cancer targeting and enhanced combinational theranostics

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