Cell cycle checkpoint defects contribute to genomic instability in PTEN deficient cells independent of DNA DSB repair

Arun Gupta, Qin Yang, Raj K. Pandita, Clayton R. Hunt, Tao Xiang, Sandeep Misri, Sicong Zeng, Julia Pagan, Jessie Jeffery, Janusz Puc, Rakesh Kumar, Zhihui Feng, Simon N. Powell, Audesh Bhat, Tomoko Yaguchi, Renu Wadhwa, Sunil C. Kaul, Ramon Parsons, Kum Kum Khanna, Tej K. Pandita

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Chromosomes in PTEN deficient cells display both numerical as well as structural alterations including regional amplification. We found that PTEN deficient cells displayed a normal DNA damage response (DDR) as evidenced by the ionizing radiation (IR)-induced phosphorylation of Ataxia Telangiectasia Mutated (ATM) as well as its effectors. PTEN deficient cells also had no defect in Rad51 expression or DNA damage repair kinetics post irradiation. In contrast, caffeine treatment specifically increased IR-induced chromosome aberrations and mitotic index only in cells with PTEN, and not in cells deficient for PTEN, suggesting that their checkpoints were defective. Furthermore, PTENdeficient cells were unable to maintain active spindle checkpoint after taxol treatment. Genomic instability in PTEN deficient cells could not be attributed to lack of PTEN at centromeres, since no interaction was detected between centromeric DNA and PTEN in wild type cells. These results indicate that PTEN deficiency alters multiple cell cycle checkpoints possibly leaving less time for DNA damage repair and/or chromosome segregation as evidenced by the increased structural as well as numerical alterations seen in PTEN deficient cells.

Original languageEnglish (US)
Pages (from-to)2198-2210
Number of pages13
JournalCell Cycle
Volume8
Issue number14
StatePublished - Jul 15 2009

Fingerprint

Genomic Instability
Cell Cycle Checkpoints
DNA Repair
DNA Damage
Ionizing Radiation
1,2-di-(4-sulfamidophenyl)-4-butylpyrazolidine-3,5-dione
Ataxia Telangiectasia
Chromosome Segregation
Mitotic Index
Centromere
Paclitaxel
Caffeine
Chromosome Aberrations
Chromosomes
Phosphorylation
DNA

Keywords

  • ATM
  • Checkpoint defects
  • DNA damage response
  • Genomic instability
  • PTEN
  • Rad51

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Gupta, A., Yang, Q., Pandita, R. K., Hunt, C. R., Xiang, T., Misri, S., ... Pandita, T. K. (2009). Cell cycle checkpoint defects contribute to genomic instability in PTEN deficient cells independent of DNA DSB repair. Cell Cycle, 8(14), 2198-2210.

Cell cycle checkpoint defects contribute to genomic instability in PTEN deficient cells independent of DNA DSB repair. / Gupta, Arun; Yang, Qin; Pandita, Raj K.; Hunt, Clayton R.; Xiang, Tao; Misri, Sandeep; Zeng, Sicong; Pagan, Julia; Jeffery, Jessie; Puc, Janusz; Kumar, Rakesh; Feng, Zhihui; Powell, Simon N.; Bhat, Audesh; Yaguchi, Tomoko; Wadhwa, Renu; Kaul, Sunil C.; Parsons, Ramon; Khanna, Kum Kum; Pandita, Tej K.

In: Cell Cycle, Vol. 8, No. 14, 15.07.2009, p. 2198-2210.

Research output: Contribution to journalArticle

Gupta, A, Yang, Q, Pandita, RK, Hunt, CR, Xiang, T, Misri, S, Zeng, S, Pagan, J, Jeffery, J, Puc, J, Kumar, R, Feng, Z, Powell, SN, Bhat, A, Yaguchi, T, Wadhwa, R, Kaul, SC, Parsons, R, Khanna, KK & Pandita, TK 2009, 'Cell cycle checkpoint defects contribute to genomic instability in PTEN deficient cells independent of DNA DSB repair', Cell Cycle, vol. 8, no. 14, pp. 2198-2210.
Gupta A, Yang Q, Pandita RK, Hunt CR, Xiang T, Misri S et al. Cell cycle checkpoint defects contribute to genomic instability in PTEN deficient cells independent of DNA DSB repair. Cell Cycle. 2009 Jul 15;8(14):2198-2210.
Gupta, Arun ; Yang, Qin ; Pandita, Raj K. ; Hunt, Clayton R. ; Xiang, Tao ; Misri, Sandeep ; Zeng, Sicong ; Pagan, Julia ; Jeffery, Jessie ; Puc, Janusz ; Kumar, Rakesh ; Feng, Zhihui ; Powell, Simon N. ; Bhat, Audesh ; Yaguchi, Tomoko ; Wadhwa, Renu ; Kaul, Sunil C. ; Parsons, Ramon ; Khanna, Kum Kum ; Pandita, Tej K. / Cell cycle checkpoint defects contribute to genomic instability in PTEN deficient cells independent of DNA DSB repair. In: Cell Cycle. 2009 ; Vol. 8, No. 14. pp. 2198-2210.
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