Pathways connecting telomeres and p53 in senescence, apoptosis, and cancer

Journal Article · Fri Jun 10 04:00:00 EDT 2005 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2005.03.211· OSTI ID:20709228

Artandi, Steven E ^[1]; Attardi, Laura D ^[2]

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1. Department of Medicine, Division of Hematology and Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305 (United Kingdom)
2. Departments of Radiation Oncology and Genetics, Stanford University School of Medicine, Stanford, CA 94305 (United Kingdom)

The ends of eukaryotic chromosomes are protected by specialized structures termed telomeres that serve in part to prevent the chromosome end from activating a DNA damage response. However, this important function for telomeres in chromosome end protection can be lost as telomeres shorten with cell division in culture or in self-renewing tissues with advancing age. Impaired telomere function leads to induction of a DNA damage response and activation of the tumor suppressor protein p53. p53 serves a critical role in enforcing both senescence and apoptotic responses to dysfunctional telomeres. Loss of p53 creates a permissive environment in which critically short telomeres are inappropriately joined to generate chromosomal end-to-end fusions. These fused chromosomes result in cycles of chromosome fusion-bridge-breakage, which can fuel cancer initiation, especially in epithelial tissues, by facilitating changes in gene copy number.

• OSTI ID: 20709228
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 331; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL DIVISION
CHROMOSOMES
DNA DAMAGES
NEOPLASMS
PROTEINS
TELOMERES