p53-Mediated apoptosis is attenuated in Werner syndrome cells

Spillare, Elisa A.; Robles, Ana I.; Wang, Xin Wei; Shen, Jiang; Yu, Chang Eu; Schellenberg, Gerard D.; Harris, Curtis C.

doi:10.1101/gad.13.11.1355

Cited by 163 publications

(140 citation statements)

References 27 publications

(26 reference statements)

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“…This nding has been con rmed and extended to show that p53 binds to the carboxyl-terminus of WRN, and that WRN is a co-activator of p53-mediated transcription (54). Similar to our ndings with XPD and XPB broblasts, we showed that p53-mediated apoptosis is attenuated in WS broblasts, as well (53). Primary broblasts from WS individuals display a characteristic premature ageing senescence phenotype in culture (55) that can interfere potentially with the induction of apoptosis.…”

Section: Recq Family Helicases: Wrn and Blmsupporting

confidence: 75%

“…Furthermore, co-microinjection of a wild-type WRN expression vector, but not a wild-type XPD expression vector, restored the sensitivity of WS broblasts to p53-mediated apoptosis. These data provide genetic evidence that WRN contributes to p53-mediated apoptosis independently of other DNA helicase(s) (53).…”

Section: Recq Family Helicases: Wrn and Blmmentioning

confidence: 64%

“…Recently, we reported that, through its carboxyl-terminus, p53 can bind to WRN in vivo and in vitro (53). This nding has been con rmed and extended to show that p53 binds to the carboxyl-terminus of WRN, and that WRN is a co-activator of p53-mediated transcription (54).…”

Section: Recq Family Helicases: Wrn and Blmmentioning

confidence: 81%

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p53-Mediated Apoptosis and Genomic Instability Diseases

Robles

2001

Acta Oncologica

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Section: Recq Family Helicases: Wrn and Blmsupporting

confidence: 75%

Section: Recq Family Helicases: Wrn and Blmmentioning

confidence: 64%

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p53-Mediated Apoptosis and Genomic Instability Diseases

Robles

2001

Acta Oncologica

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“…Interestingly, hp150 is not the first common interaction partner of WRN and BLM. BLM and WRN both interact with replication protein A (RPA) (Garcia et al, 2004;Doherty et al, 2005), p53 (Spillare et al, 1999;Wang et al, 2001;Yang et al, 2002), flap endonuclease-1 (FEN-1) (Sharma et al, 2004a, b) and TRF2 Bradshaw et al, 2005). Moreover, BLM and WRN also interact with each other .…”

Section: Discussionmentioning

confidence: 99%

The Werner syndrome protein is required for recruitment of chromatin assembly factor 1 following DNA damage

et al. 2006

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The Werner syndrome protein (WRN) and chromatin assembly factor 1 (CAF-1) are both involved in the maintenance of genome stability. In response to DNAdamaging signals, both of these proteins relocate to sites where DNA synthesis occurs. However, the interaction between WRN and CAF-1 has not yet been investigated. In this report, we show that WRN interacts physically with the largest subunit of CAF-1, hp150, in vitro and in vivo. Although hp150 does not alter WRN catalytic activities in vitro, and the chromatin assembly activity of CAF-1 is not affected in the absence of WRN in vivo, this interaction may have an important role during the cellular response to DNA replication fork blockage and/or DNA damage signals. In hp150 RNA-mediated interference (RNAi) knockdown cells, WRN partially formed foci following hydroxyurea (HU) treatment. However, in the absence of WRN, hp150 did not relocate to form foci following exposure to HU and ultraviolet light. Thus, our results demonstrate that WRN responds to DNA damage before CAF-1 and suggest that WRN may recruit CAF-1, via interaction with hp150, to DNA damage sites during DNA synthesis.

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“…GM01310, a normal human lymphoblastoid cell line (LCL), and WI-38, normal human fibroblasts were obtained from the ATCC. Western blot analyses and immunoprecipitation were essentially as described previously (Spillare et al, 1999). Briefly, cell extracts were prepared in lysis buffer containing 50 mM Tris-HCl (pH 7.5), 120 mM NaCl, 1% Nonidet P-40 with protease inhibitors.…”

Section: Methodsmentioning

confidence: 99%

The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase

et al. 2004

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The human MSH2/6 complex is essential for mismatch recognition during the repair of replication errors. Although mismatch repair components have been implicated in DNA homologous recombination repair, the exact function of hMSH2/6 in this pathway is unclear. Here, we show that the recombinant hMSH2/6 protein complex stimulated the ability of the Bloom's syndrome gene product, BLM, to process Holliday junctions in vitro, an activity that could also be regulated by p53. Consistent with these observations, hMSH6 colocalized with BLM and phospho-ser15-p53 in hydroxyurea-induced RAD51 nuclear foci that may correspond to the sites of presumed stalled DNA replication forks and more likely the resultant DNA double-stranded breaks. In addition, we show that hMSH2 and hMSH6 coimmunoprecipitated with BLM, p53, and RAD51. Both the number of RAD51 foci and the amount of the BLM-p53-RAD51 complex are increased in hMSH2-or hMSH6-deficient cells. These data suggest that hMSH2/6 formed a complex with BLM-p53-RAD51 in response to the damaged DNA forks during double-stranded break repair.

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p53-Mediated apoptosis is attenuated in Werner syndrome cells

Cited by 163 publications

References 27 publications

p53-Mediated Apoptosis and Genomic Instability Diseases

p53-Mediated Apoptosis and Genomic Instability Diseases

The Werner syndrome protein is required for recruitment of chromatin assembly factor 1 following DNA damage

The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase

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