NASA Logo

NTRS

NTRS - NASA Technical Reports Server

Back to Results
Gene conversion is strongly induced in human cells by double-strand breaks and is modulated by the expression of BCL-x(L)Homology-directed repair (HDR) of DNA double-strand breaks (DSBs) contributes to the maintenance of genomic stability in rodent cells, and it has been assumed that HDR is of similar importance in DSB repair in human cells. However, some outcomes of homologous recombination can be deleterious, suggesting that factors exist to regulate HDR. We demonstrated previously that overexpression of BCL-2 or BCL-x(L) enhanced the frequency of X-ray-induced TK1 mutations, including loss of heterozygosity events presumed to arise by mitotic recombination. The present study was designed to test whether HDR is a prominent DSB repair pathway in human cells and to determine whether ectopic expression of BCL-x(L) affects HDR. Using TK6-neo cells, we find that a single DSB in an integrated HDR reporter stimulates gene conversion 40-50-fold, demonstrating efficient DSB repair by gene conversion in human cells. Significantly, DSB-induced gene conversion events are 3-4-fold more frequent in TK6 cells that stably overexpress the antiapoptotic protein BCL-X(L). Thus, HDR plays an important role in maintaining genomic integrity in human cells, and ectopic expression of BCL-x(L) enhances HDR of DSBs. This is the first study to highlight a function for BCL-x(L) in modulating DSB repair in human cells.
Document ID
20040088416
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Wiese, Claudia
(Lawrence Berkeley National Laboratory Berkeley, California 94720, United States)
Pierce, Andrew J.
Gauny, Stacey S.
Jasin, Maria
Kronenberg, Amy
Chatterjee, A.
Date Acquired
August 21, 2013
Publication Date
March 1, 2002
Publication Information
Publication: Cancer research
Volume: 62
Issue: 5
ISSN: 0008-5472
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: CA 73966
CONTRACT_GRANT: GM54688
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Radiation Health
Non-NASA Center

Available Downloads

There are no available downloads for this record.
No Preview Available