Journal Article

Reduced apoptotic response to camptothecin in CHO cells deficient in XRCC3

John M. Hinz, Thomas Helleday and Mark Meuth

in Carcinogenesis

Volume 24, issue 2, pages 249-253
Published in print February 2003 | ISSN: 0143-3334
Published online February 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/24.2.249
Reduced apoptotic response to camptothecin in CHO cells deficient in XRCC3

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

Eukaryotic cells respond to DNA damage by activation of DNA repair, cell-cycle arrest and apoptosis. Several reports suggest that such responses may be coordinated by communication between damage repair proteins and proteins signalling other cellular responses. The Rad51-guided homologous recombination (HR) repair plays an important role in recognition and repair of DNA double-strand breaks (DSBs) and cells deficient in this repair pathway become hypersensitive to agents that induce DSBs. In the work reported here we investigated the possible role of the Rad51-like HR proteins XRCC2, XRCC3 and Rad51C in apoptosis following the induction of DSBs by camptothecin. We show that a hamster cell line (irs1SF) deficient in the HR repair gene XRCC3 exhibits altered death and cell-cycle checkpoint responses following treatment with growth inhibitory concentrations of camptothecin. In contrast, hamster cells defective in XRCC2 (irs1) or Rad51C (irs3) treated with equally toxic doses of this agent exhibit a rapid induction of apoptosis similar to that seen in the parental cell line or mutant cells corrected for the HR defect. These results suggest that XRCC3 activity may be necessary for efficient entry into apoptosis in response to DSBs.

Keywords: CHO, Chinese hamster ovary; CPT, camptothecin; DSBs, DNA double-strand breaks; HR, homologous recombination; NHEJ, non-homologous end joining; PI, propidium iodide.

Journal Article.  4070 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.