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A unique role of the DNA fragmentation factor in maintaining genomic stability.

Publication ,  Journal Article
Yan, B; Wang, H; Peng, Y; Hu, Y; Wang, H; Zhang, X; Chen, Q; Bedford, JS; Dewhirst, MW; Li, C-Y
Published in: Proc Natl Acad Sci U S A
January 31, 2006

DNA fragmentation is a hallmark of apoptosis (programmed cell death). However, the biological function of apoptotic DNA fragmentation remains unclear. Here, we show that DNA fragmentation factor plays an important role for maintaining genomic stability. Inhibition or loss of the DNA fragmentation factor (DFF)/caspase-activated DNase (CAD), whose nuclease activity is responsible for digesting genomic DNA during apoptosis, led to significant increases in spontaneous or induced gene mutations, gene amplifications, and chromosomal instability in primary mouse cells and transformed human cell lines. The mechanism underlying genetic instability in DFF/CAD-deficient cells, at least in part, involves a small but significant elevation in the survival of cells exposed to ionizing radiation, suggesting that apoptotic DNA fragmentation factor contributes to genomic stability by ensuring the removal of cells that have suffered DNA damage. In support of this hypothesis are the observations of increased cellular transformation of mouse embryonic cells from the DFF/CAD-null mice and significantly enhanced susceptibility to radiation-induced carcinogenesis in these mice. These data, in combination with published reports on the existence of tumor-specific gene mutations/deletions in the DFF/CAD genes in human cancer samples, suggest that apoptotic DNA fragmentation factor is required for the maintenance of genetic stability and may play a role in tumor suppression.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

January 31, 2006

Volume

103

Issue

5

Start / End Page

1504 / 1509

Location

United States

Related Subject Headings

  • Transgenes
  • Time Factors
  • Plasmids
  • Neoplasms, Radiation-Induced
  • Neoplasms
  • Mutation
  • Mice, Transgenic
  • Mice
  • Humans
  • Genome
 

Citation

APA
Chicago
ICMJE
MLA
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Yan, B., Wang, H., Peng, Y., Hu, Y., Zhang, X., Chen, Q., … Li, C.-Y. (2006). A unique role of the DNA fragmentation factor in maintaining genomic stability. Proc Natl Acad Sci U S A, 103(5), 1504–1509. https://doi.org/10.1073/pnas.0507779103
Yan, Bin, Huili Wang, Yuanlin Peng, Ye Hu, He Wang, Xiuwu Zhang, Qi Chen, Joel S. Bedford, Mark W. Dewhirst, and Chuan-Yuan Li. “A unique role of the DNA fragmentation factor in maintaining genomic stability.Proc Natl Acad Sci U S A 103, no. 5 (January 31, 2006): 1504–9. https://doi.org/10.1073/pnas.0507779103.
Yan B, Wang H, Peng Y, Hu Y, Zhang X, Chen Q, et al. A unique role of the DNA fragmentation factor in maintaining genomic stability. Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1504–9.
Yan, Bin, et al. “A unique role of the DNA fragmentation factor in maintaining genomic stability.Proc Natl Acad Sci U S A, vol. 103, no. 5, Jan. 2006, pp. 1504–09. Pubmed, doi:10.1073/pnas.0507779103.
Yan B, Wang H, Peng Y, Hu Y, Zhang X, Chen Q, Bedford JS, Dewhirst MW, Li C-Y. A unique role of the DNA fragmentation factor in maintaining genomic stability. Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1504–1509.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

January 31, 2006

Volume

103

Issue

5

Start / End Page

1504 / 1509

Location

United States

Related Subject Headings

  • Transgenes
  • Time Factors
  • Plasmids
  • Neoplasms, Radiation-Induced
  • Neoplasms
  • Mutation
  • Mice, Transgenic
  • Mice
  • Humans
  • Genome