DNA Repair Factor APLF Is a Histone Chaperone

Mehrotra, Pawan Vinod; Ahel, Dragana; Ryan, Daniel P.; Weston, Ria; Wiechens, Nicola; Kraehenbuehl, Rolf; Owen-Hughes, Tom; Ahel, Ivan

doi:10.1016/j.molcel.2010.12.008

Cited by 138 publications

(125 citation statements)

References 26 publications

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“…As a histone chaperone, SET/TAF-Iβ associates to core histones to shield their positive charge, preventing improper contact with DNA and facilitating the correct deposition of free histones onto DNA for nucleosome formation (5). Recent work points to the crucial role of chromatin dynamics in DNA damage response (6)(7)(8). In fact, histone chaperones have emerged as key players in the transient disorganization of chromatin required in the DNA repair process.…”

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confidence: 99%

“…In fact, histone chaperones have emerged as key players in the transient disorganization of chromatin required in the DNA repair process. Thus, the histone chaperones aprataxin-PNK-like factor (APLF) (6), antisilencing function 1 (Asf1) (9), chromatin assembly factor 1 (CAF-1) (10), death domain-associated protein 6 (DAXX) (11), facilitating chromatin transcription (FACT) (12), histone regulator A (HIRA) (13), nucleolin (14), p400 (15), and nucleosome assembly protein 1-like 1 (NAP1L1) and 1-like 4 (NAP1L4) (7) are recruited to damaged chromatin, thereby promoting histone dynamics in response to DNA damage. Recently, SET/TAF-1β was found to be recruited to DNA breaks to modulate the DNA damage response through the retention of certain chromatin proteins, resulting in chromatin compaction (16).…”

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confidence: 99%

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Structural basis for inhibition of the histone chaperone activity of SET/TAF-Iβ by cytochrome c

González‐Arzola

Dı́az-Moreno

Cano-González

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

114

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Chromatin is pivotal for regulation of the DNA damage process insofar as it influences access to DNA and serves as a DNA repair docking site. Recent works identify histone chaperones as key regulators of damaged chromatin’s transcriptional activity. However, understanding how chaperones are modulated during DNA damage response is still challenging. This study reveals that the histone chaperone SET/TAF-Iβ interacts with cytochrome c following DNA damage. Specifically, cytochrome c is shown to be translocated into cell nuclei upon induction of DNA damage, but not upon stimulation of the death receptor or stress-induced pathways. Cytochrome c was found to competitively hinder binding of SET/TAF-Iβ to core histones, thereby locking its histone-binding domains and inhibiting its nucleosome assembly activity. In addition, we have used NMR spectroscopy, calorimetry, mutagenesis, and molecular docking to provide an insight into the structural features of the formation of the complex between cytochrome c and SET/TAF-Iβ. Overall, these findings establish a framework for understanding the molecular basis of cytochrome c-mediated blocking of SET/TAF-Iβ, which subsequently may facilitate the development of new drugs to silence the oncogenic effect of SET/TAF-Iβ’s histone chaperone activity.

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mentioning

confidence: 99%

mentioning

confidence: 99%

Structural basis for inhibition of the histone chaperone activity of SET/TAF-Iβ by cytochrome c

González‐Arzola

Dı́az-Moreno

Cano-González

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

114

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“…MacroH2A.1 is a repressive mark that is associated with inactive chromatin, and earlier studies have demonstrated that isoforms of the histone variant MacroH2A can act as a barrier to the reprogramming of fibroblasts to iPSCs (GasparMaia et al, 2013). APLF can recruit the MacroH2A.1 histone variant in response to DNA damage induced by lasers (Mehrotra et al, 2011). We studied whether knockdown of APLF could suppress MacroH2A.1 incorporation at the chromatin level and hence whether this might be responsible for the more efficient reprogramming of MEFs.…”

Section: Aplf Regulates Genes That Are Implicated In Met During the Gmentioning

confidence: 99%

“…In this study, we observed that the expression of the newly found histone chaperone APLF was lower in embryonic stem cells (ESCs) than in mouse embryonic fibroblasts (MEFs). APLF is a recognized DNAdamage-specific histone chaperone, and it could interact with a histones H3 and H4 tetramer or could recruit variants of H2A to the damaged sites (Mehrotra et al, 2011). However, the role of APLF in reprogramming or any other aspect of developmental biology has never been considered.…”

Section: Introductionmentioning

confidence: 99%

Histone chaperone APLF regulates induction of pluripotency in murine fibroblasts

Syed

Joseph

Mukherjee³

et al. 2016

Journal of Cell Science

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The authors apologise to the readers for any confusion that this error might have caused. For the first time, we report here that the downregulation of histone chaperone Aprataxin PNK-like factor (APLF) promotes reprogramming by augmenting the expression of E-cadherin (Cdh1), which is implicated in the mesenchymal-to-epithelial transition (MET) involved in the generation of induced pluripotent stem cells (iPSCs) from mouse embryonic fibroblasts (MEFs). Downregulation of APLF in MEFs expedites the loss of the repressive MacroH2A.1 (encoded by H2afy) histone variant from the Cdh1 promoter and enhances the incorporation of active histone H3me2K4 marks at the promoters of the pluripotency genes Nanog and Klf4, thereby accelerating the process of cellular reprogramming and increasing the efficiency of iPSC generation. We demonstrate a new histone chaperone (APLF)-MET-histone modification cohort that functions in the induction of pluripotency in fibroblasts. This regulatory axis might provide new mechanistic insights into perspectives of epigenetic regulation involved in cancer metastasis.

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“…PNK-and APTX-like FHA protein (PALF, also known as APLF, C2orf13 or Xip1) has AP endonuclease activity (Kanno et al, 2007;Iles et al, 2007). Recent study showed that APLF also has histone chaperone activity (Mehrotra et al, 2011) and that it co-operates with PARP-3, which is newly found as a DSB sensor (Rulten et al, 2011). It might be noted that all of these factors bears BRCT or FHA domain as module to bind phosphorylated proteins.…”

Section: Processing Enzymesmentioning

confidence: 99%

DNA Double-Strand Break Repair Through Non-Homologous End-Joining: Recruitment and Assembly of the Players

Kamdar¹,

Matsumoto²

2011

DNA Repair

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DNA double-strand break repair through non-homologous end-joining pathway Homologous Recombination and Non-Homologous End-JoiningHR is a reaction wherein the genetic material is exchanged between two similar or identical strands of DNA. In the repair of DSB through HR, undamaged DNA serves as a template to reconsitute the original sequence across the break. On the other hand, NHEJ is the direct rejoining of the broken DNA ends without much regard for homology at these ends.www.intechopen.com DNA Repair 478Therefore, NHEJ may sometimes incur nucleotide deletions or insertions at the junction or joining with incorrect partner, leading to chromosomal abberations like duplications, inversions or translocations. Hence it is considered that NHEJ is less accurate than HR but, nevertheless, important especially in vertebrates. In HR, the template should be found in homologous chromosome or in sister chromatid. Organisms like budding yeast can avail homologous chromosome as the template. However, vertebrate can utilize only sister chromatid, but not homologous chromosome, as the template for HR and, therefore, the repair of DSB through HR is limited to late S and G2 phases. The majolity of the cells reside in G0 or G1 phases in vertebrate body, where only NHEJ can operate. Additionally, only small portions of the genome in vertebrate are encoding protein or functional RNA and other portions are intervening or repetitive sequences. These regions may have important roles in the structural maintenance of the genome, proper replication/segregation of the genome or spatiotemporal regulation of the genen expression. Nevertheless, small deletion or insertion of nucleotides might be tolerated in most portion of the vertebrate genome. Finally, whereas HR is utilized in meiotic recombination in reproductive organs, NHEJ is utilized in V(D)J recombination in immune system to establish diversity of immunogloblins and T cell recepters. Thus, genetic defect in either one of NHEJ components results not only in elevated sensitivity toward radiation and radiomimetic agents but also in immunodeficiency.

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DNA Repair Factor APLF Is a Histone Chaperone

Cited by 138 publications

References 26 publications

Structural basis for inhibition of the histone chaperone activity of SET/TAF-Iβ by cytochrome c

Structural basis for inhibition of the histone chaperone activity of SET/TAF-Iβ by cytochrome c

Histone chaperone APLF regulates induction of pluripotency in murine fibroblasts

DNA Double-Strand Break Repair Through Non-Homologous End-Joining: Recruitment and Assembly of the Players

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