DNA Damage Triggers Golgi Dispersal via DNA-PK and GOLPH3

Farber-Katz, Suzette; Dippold, Holly C.; Buschman, Matthew D.; Peterman, Marshall C.; Xing, Mengke; Noakes, Christopher; Tat, John; Ng, Minna; Rahajeng, Juliati; Cowan, David M.; Fuchs, Greg J.; Zhou, Huilin; Field, Seth J.

doi:10.1016/j.cell.2013.12.023

Cited by 198 publications

(298 citation statements)

References 60 publications

(94 reference statements)

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“…Screens for S/TQ-containing substrates of ATR and ATM following DNA damage have also revealed putative substrates outside of the nucleus, as well as factors that are not directly linked to DNA repair processes (Matsuoka et al, 2007;Mu et al, 2007;Paulsen et al, 2009), although the functional relevance of many of these phosphorylation events remains to be determined. Intriguingly, DNA-PK has also been located at the Golgi, reinforcing the possibility that other PIKKs might also function outside of the nucleus (Farber-Katz et al, 2014).…”

Section: Signaling Outputs Of Atr and Atmmentioning

confidence: 99%

ATM and ATR signaling at a glance

Awasthi

Foiani

Kumar

2015

Journal of Cell Science

232

228

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There was an error published in J. Cell Sci. 128, 4255-4262.An incorrect citation and reference was given for the last sentence in Box 2. The correct citation and reference are: A recent review provides a detailed update on ATM and ATR inhibitors, and their potential as drug targets (Weber and Ryan, 2015).Weber, A.M. and Ryan, A.J. (2015). ATM and ATR as therapeutic targets in cancer. Pharmacol Ther. 149, 124-138.The authors apologise to the readers for any confusion that this error might have caused. Although the role of both ATM and ATR in DNA repair, cell cycle regulation and apoptosis have been well studied, both still remain in the focus of current research activities owing to their role in cancer. Recent advances in the field suggest that these proteins have an additional function in maintaining cellular homeostasis under both stressed and non-stressed conditions. In this Cell Science at a Glance article and the accompanying poster, we present an overview of recent advances in ATR and ATM research with emphasis on that into the modes of ATM and ATR activation, the different signaling pathways they participate in -including those that do not involve DNA damage -and highlight their relevance in cancer. 1285

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Section: Signaling Outputs Of Atr and Atmmentioning

confidence: 99%

ATM and ATR signaling at a glance

Awasthi

Foiani

Kumar

2015

Journal of Cell Science

232

228

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“…31 Recently, a study demonstrated that, in mammalian mitotic cells, DNA damage triggers the Golgi to fragment and disperse throughout the cytoplasm leading to the amplification of the DNA damage response via the DNA damage protein kinase, DNA-PK. 32 This study highlights direct links between the DNA damage response and the Golgi. Thus, the presence of FANCB, FANCM and FANCD2 proteins in the Golgi raised the possibility that the newly synthesized FANC proteins may undergo post-translational modification and store for a period of time prior to being distributed to sites of DNA damage foci at appropriate time points of germ cell development.…”

Section: Discussionmentioning

confidence: 99%

Uncoupling of transcription and translation of Fanconi anemia (FANC) complex proteins during spermatogenesis

et al. 2014

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Male germ cell genome integrity is critical for spermatogenesis, fertility and normal development of the offspring. Several DNA repair pathways exist in male germ cells. One such important pathway is the Fanconi anemia (FANC) pathway. Unlike in somatic cells, expression profiles and the role of the FANC pathway in germ cells remain largely unknown. In this study, we undertook an extensive expression analyses at both mRNA and protein levels of key components of the FANC pathway during spermatogenesis in the mouse. Herein we show that Fanc mRNAs and proteins displayed developmental enrichment within particular male germ cell types. Spermatogonia and pre-leptotene spermatocytes contained the majority of the FANC components examined i.e. complex I members FANCB, FANCG and FANCM, complex II members FANCD2 and FANCI, and complex III member FANCJ. Leptotene, zygotene and early pachytene spermatocytes contained FANCB, FANCG, FANCM and FANCD2. With the exception of FANCL, all FANC proteins examined were not detected in round spermatids. Elongating and elongated spermatids contained FANCB, FANCG, FANCL and FANCJ. qPCR analysis on isolated spermatocytes and round spermatids showed that Fancg, Fancl, Fancm, Fancd2, Fanci and Fancj mRNAs were expressed in both of these germ cell types, indicating that some degree of translational repression of these FANC proteins occurs during the transition from meiosis to spermiogenesis. Taken together, our findings raise the possibility that the assembly of FANC protein complexes in each of the male germ cell type is unique and may be distinct from the proposed model in mitotic cells.

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“…GOLPH3 bridges phosphatidylinositol-4-phosphate and actomyosin and thereby drives Golgi dispersal and vesicular budding (3,38). A PITPNC1/ RAB1B protein complex anchors GOLPH3 to the Golgi, facilitating Golgi extension and the release of secretory vesicles containing factors that promote extracellular matrix remodeling and tumor angiogenesis (4).…”

Section: Discussionmentioning

confidence: 99%