A role for PML, and the nuclear body in genomic stability

Sue Zhong, Hu Peng, Tian Zhang Ye, Rodica Stan, Nathan Ellis, Pier Paolo Pandolfi

Research output: Contribution to journalArticle

182 Citations (Scopus)

Abstract

The PML gene of acute promyelocytic leukemia (APL) encodes a cell-growth and tumour suppressor. PML localizes to discrete nuclear bodies (NBs) that are disrupted in APL cells. The Bloom syndrome gene BLM encodes a RecQ DNA helicase, whose absence from the cell results in genomic instability epitomized by high levels of sister-chromatid exchange (SCE) and cancer predisposition. We show here that BLM colocalizes with PML to the NB. In cells from persons with Bloom syndrome the localization of PML is unperturbed, whereas in APL cells carrying the PML-RARα oncoprotein, both PML and BLM are delocalized from the NB into microspeckled nuclear regions. Treatment with retinoic acid (RA) induces the relocalization of both proteins to the NE. In primary PML-/- cells, BLM fails to accumulate in the NB. Strikingly, in PML-/- cells the frequency of SCEs is increased relative to PML+/+ cells. These data demonstrate that BLM is a constituent of the NB and that PML is required for its accumulation in these nuclear domains and for the normal function of BLM. Thus, our findings suggest a role for BLM in APL pathogenesis and implicate the PML NB in the maintenance of genomic stability.

Original languageEnglish (US)
Pages (from-to)7941-7947
Number of pages7
JournalOncogene
Volume18
Issue number56
StatePublished - Dec 23 1999
Externally publishedYes

Fingerprint

Genomic Instability
Acute Promyelocytic Leukemia
Bloom Syndrome
RecQ Helicases
DNA Helicases
Sister Chromatid Exchange
Oncogene Proteins
Tretinoin
Genes
Neoplasms
Maintenance
Growth

Keywords

  • APL
  • BLM
  • Bloom syndrome
  • Nuclear body
  • PML
  • Sister-chromatid exchange

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Zhong, S., Peng, H., Ye, T. Z., Stan, R., Ellis, N., & Pandolfi, P. P. (1999). A role for PML, and the nuclear body in genomic stability. Oncogene, 18(56), 7941-7947.

A role for PML, and the nuclear body in genomic stability. / Zhong, Sue; Peng, Hu; Ye, Tian Zhang; Stan, Rodica; Ellis, Nathan; Pandolfi, Pier Paolo.

In: Oncogene, Vol. 18, No. 56, 23.12.1999, p. 7941-7947.

Research output: Contribution to journalArticle

Zhong, S, Peng, H, Ye, TZ, Stan, R, Ellis, N & Pandolfi, PP 1999, 'A role for PML, and the nuclear body in genomic stability', Oncogene, vol. 18, no. 56, pp. 7941-7947.
Zhong S, Peng H, Ye TZ, Stan R, Ellis N, Pandolfi PP. A role for PML, and the nuclear body in genomic stability. Oncogene. 1999 Dec 23;18(56):7941-7947.
Zhong, Sue ; Peng, Hu ; Ye, Tian Zhang ; Stan, Rodica ; Ellis, Nathan ; Pandolfi, Pier Paolo. / A role for PML, and the nuclear body in genomic stability. In: Oncogene. 1999 ; Vol. 18, No. 56. pp. 7941-7947.
@article{58f0a6b0c25544bb9feb629ec4b52aa1,
title = "A role for PML, and the nuclear body in genomic stability",
abstract = "The PML gene of acute promyelocytic leukemia (APL) encodes a cell-growth and tumour suppressor. PML localizes to discrete nuclear bodies (NBs) that are disrupted in APL cells. The Bloom syndrome gene BLM encodes a RecQ DNA helicase, whose absence from the cell results in genomic instability epitomized by high levels of sister-chromatid exchange (SCE) and cancer predisposition. We show here that BLM colocalizes with PML to the NB. In cells from persons with Bloom syndrome the localization of PML is unperturbed, whereas in APL cells carrying the PML-RARα oncoprotein, both PML and BLM are delocalized from the NB into microspeckled nuclear regions. Treatment with retinoic acid (RA) induces the relocalization of both proteins to the NE. In primary PML-/- cells, BLM fails to accumulate in the NB. Strikingly, in PML-/- cells the frequency of SCEs is increased relative to PML+/+ cells. These data demonstrate that BLM is a constituent of the NB and that PML is required for its accumulation in these nuclear domains and for the normal function of BLM. Thus, our findings suggest a role for BLM in APL pathogenesis and implicate the PML NB in the maintenance of genomic stability.",
keywords = "APL, BLM, Bloom syndrome, Nuclear body, PML, Sister-chromatid exchange",
author = "Sue Zhong and Hu Peng and Ye, {Tian Zhang} and Rodica Stan and Nathan Ellis and Pandolfi, {Pier Paolo}",
year = "1999",
month = "12",
day = "23",
language = "English (US)",
volume = "18",
pages = "7941--7947",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "56",

}

TY - JOUR

T1 - A role for PML, and the nuclear body in genomic stability

AU - Zhong, Sue

AU - Peng, Hu

AU - Ye, Tian Zhang

AU - Stan, Rodica

AU - Ellis, Nathan

AU - Pandolfi, Pier Paolo

PY - 1999/12/23

Y1 - 1999/12/23

N2 - The PML gene of acute promyelocytic leukemia (APL) encodes a cell-growth and tumour suppressor. PML localizes to discrete nuclear bodies (NBs) that are disrupted in APL cells. The Bloom syndrome gene BLM encodes a RecQ DNA helicase, whose absence from the cell results in genomic instability epitomized by high levels of sister-chromatid exchange (SCE) and cancer predisposition. We show here that BLM colocalizes with PML to the NB. In cells from persons with Bloom syndrome the localization of PML is unperturbed, whereas in APL cells carrying the PML-RARα oncoprotein, both PML and BLM are delocalized from the NB into microspeckled nuclear regions. Treatment with retinoic acid (RA) induces the relocalization of both proteins to the NE. In primary PML-/- cells, BLM fails to accumulate in the NB. Strikingly, in PML-/- cells the frequency of SCEs is increased relative to PML+/+ cells. These data demonstrate that BLM is a constituent of the NB and that PML is required for its accumulation in these nuclear domains and for the normal function of BLM. Thus, our findings suggest a role for BLM in APL pathogenesis and implicate the PML NB in the maintenance of genomic stability.

AB - The PML gene of acute promyelocytic leukemia (APL) encodes a cell-growth and tumour suppressor. PML localizes to discrete nuclear bodies (NBs) that are disrupted in APL cells. The Bloom syndrome gene BLM encodes a RecQ DNA helicase, whose absence from the cell results in genomic instability epitomized by high levels of sister-chromatid exchange (SCE) and cancer predisposition. We show here that BLM colocalizes with PML to the NB. In cells from persons with Bloom syndrome the localization of PML is unperturbed, whereas in APL cells carrying the PML-RARα oncoprotein, both PML and BLM are delocalized from the NB into microspeckled nuclear regions. Treatment with retinoic acid (RA) induces the relocalization of both proteins to the NE. In primary PML-/- cells, BLM fails to accumulate in the NB. Strikingly, in PML-/- cells the frequency of SCEs is increased relative to PML+/+ cells. These data demonstrate that BLM is a constituent of the NB and that PML is required for its accumulation in these nuclear domains and for the normal function of BLM. Thus, our findings suggest a role for BLM in APL pathogenesis and implicate the PML NB in the maintenance of genomic stability.

KW - APL

KW - BLM

KW - Bloom syndrome

KW - Nuclear body

KW - PML

KW - Sister-chromatid exchange

UR - http://www.scopus.com/inward/record.url?scp=0033598931&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033598931&partnerID=8YFLogxK

M3 - Article

C2 - 10637504

AN - SCOPUS:0033598931

VL - 18

SP - 7941

EP - 7947

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 56

ER -