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ATM regulates a DNA damage response posttranscriptional RNA operon in lymphocytes.

Publication ,  Journal Article
Mazan-Mamczarz, K; Hagner, PR; Zhang, Y; Dai, B; Lehrmann, E; Becker, KG; Keene, JD; Gorospe, M; Liu, Z; Gartenhaus, RB
Published in: Blood
February 24, 2011

Maintenance of genomic stability depends on the DNA damage response, a biologic barrier in early stages of cancer development. Failure of this response results in genomic instability and high predisposition toward lymphoma, as seen in patients with ataxia-telangiectasia mutated (ATM) dysfunction. ATM activates multiple cell-cycle checkpoints and DNA repair after DNA damage, but its influence on posttranscriptional gene expression has not been examined on a global level. We show that ionizing radiation modulates the dynamic association of the RNA-binding protein HuR with target mRNAs in an ATM-dependent manner, potentially coordinating the genotoxic response as an RNA operon. Pharmacologic ATM inhibition and use of ATM-null cells revealed a critical role for ATM in this process. Numerous mRNAs encoding cancer-related proteins were differentially associated with HuR depending on the functional state of ATM, in turn affecting expression of encoded proteins. The findings presented here reveal a previously unidentified role of ATM in controlling gene expression posttranscriptionally. Dysregulation of this DNA damage response RNA operon is probably relevant to lymphoma development in ataxia-telangiectasia persons. These novel RNA regulatory modules and genetic networks provide critical insight into the function of ATM in oncogenesis.

Duke Scholars

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

February 24, 2011

Volume

117

Issue

8

Start / End Page

2441 / 2450

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Radiation, Ionizing
  • RNA-Binding Proteins
  • RNA, Messenger
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Operon
  • Mutant Proteins
  • Lymphoma
  • Lymphocytes
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Mazan-Mamczarz, K., Hagner, P. R., Zhang, Y., Dai, B., Lehrmann, E., Becker, K. G., … Gartenhaus, R. B. (2011). ATM regulates a DNA damage response posttranscriptional RNA operon in lymphocytes. Blood, 117(8), 2441–2450. https://doi.org/10.1182/blood-2010-09-310987
Mazan-Mamczarz, Krystyna, Patrick R. Hagner, Yongqing Zhang, Bojie Dai, Elin Lehrmann, Kevin G. Becker, Jack D. Keene, Myriam Gorospe, Zhenqui Liu, and Ronald B. Gartenhaus. “ATM regulates a DNA damage response posttranscriptional RNA operon in lymphocytes.Blood 117, no. 8 (February 24, 2011): 2441–50. https://doi.org/10.1182/blood-2010-09-310987.
Mazan-Mamczarz K, Hagner PR, Zhang Y, Dai B, Lehrmann E, Becker KG, et al. ATM regulates a DNA damage response posttranscriptional RNA operon in lymphocytes. Blood. 2011 Feb 24;117(8):2441–50.
Mazan-Mamczarz, Krystyna, et al. “ATM regulates a DNA damage response posttranscriptional RNA operon in lymphocytes.Blood, vol. 117, no. 8, Feb. 2011, pp. 2441–50. Pubmed, doi:10.1182/blood-2010-09-310987.
Mazan-Mamczarz K, Hagner PR, Zhang Y, Dai B, Lehrmann E, Becker KG, Keene JD, Gorospe M, Liu Z, Gartenhaus RB. ATM regulates a DNA damage response posttranscriptional RNA operon in lymphocytes. Blood. 2011 Feb 24;117(8):2441–2450.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

February 24, 2011

Volume

117

Issue

8

Start / End Page

2441 / 2450

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Radiation, Ionizing
  • RNA-Binding Proteins
  • RNA, Messenger
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Operon
  • Mutant Proteins
  • Lymphoma
  • Lymphocytes