Telomere-dependent and telomere-independent origins of endogenous DNA damage in tumor cells.

Abstract:

:Human tumors and cultured cells contain elevated levels of endogenous DNA damage resulting from telomere dysfunction, replication and transcription errors, reactive oxygen species, and genome instability. However, the contribution of telomere-associated versus telomere-independent endogenous DNA lesions to this damage has never been examined. In this study, we characterized the relative amounts of these two types of DNA damage in five tumor cell lines by noting whether gamma-H2AX foci, generally considered to mark DNA double-strand breaks (DSBs), were on chromosome arms or at chromosome ends. We found that while the numbers of non-telomeric DSBs were remarkably similar in these cultures, considerable variation was detected in the level of telomeric damage. The distinct heterogeneity in the numbers of gamma-H2AX foci in these tumor cell lines was found to be due to foci associated with uncapped telomeres, and the amount of total telomeric damage also appeared to inversely correlate with the telomerase activity present in these cells. These results indicate that damaged telomeres are the major factor accounting for the variability in the amount of DNA DSB damage in tumor cells. This characterization of DNA damage in tumor cells helps clarify the contribution of non-telomeric DSBs and damaged telomeres to major genomic alterations.

journal_name

Aging (Albany NY)

journal_title

Aging

authors

Nakamura AJ,Redon CE,Bonner WM,Sedelnikova OA

doi

10.18632/aging.100019

subject

Has Abstract

pub_date

2009-02-04 00:00:00

pages

212-8

issue

2

issn

1945-4589

journal_volume

1

pub_type

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