JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
Add like
Add dislike
Add to saved papers

Severe combined immunodeficient cells expressing mutant hRAD54 exhibit a marked DNA double-strand break repair and error-prone chromosome repair defect.

Cancer Research 2001 March 16
DNA double-strand breaks (DSBs) can be induced by a number of endogenous and exogenous agents and are lethal events if left unrepaired. DNA DSBs can be repaired by homologous recombination (HR) and nonhomologous end joining (NHEJ). In mammals and higher eukaryotes, NHEJ is thought to be the primary pathway for repair, but the role for each pathway in DNA DSB repair has not been fully elucidated. To define the relative contributions of HR and NHEJ in mammalian DNA DSB repair, cells defective in both pathways were produced. Double-mutant cells were created by expressing a dominant mutant hRAD54 protein in a DNA-dependent protein kinase (DNA-PK)-deficient severe combined immunodeficient cell line. Double-mutant cells demonstrate an increase in ionizing radiation sensitivity and a decrease in DNA DSB repair as compared with either single mutant, whereas single-mutant hRAD54 cells exhibit a wild-type phenotype. Unexpectedly, DNA-PK-null cells were more resistant to mitomycin-C damage than were wild-type cells. Chromosome aberration analysis reveals numerous incomplete chromatid exchange aberrations in the majority of the double-mutant cells after ionizing radiation exposure. Our findings confirm a role for HR in DSB repair in higher eukaryotes, yet indicate that its role is not evident unless the primary repair pathway, NHEJ, is nonfunctional. Mitomycin-C resistance in DNA-PK-null cells compared with wild-type cells suggests that the HR pathway may be more efficient in cross-link repair in the absence of NHEJ. Lastly, the incorrectly repaired chromatid damage observed in double-mutant cells may result from failed recombination or another error-prone repair process that is apparent in the absence of the two primary repair pathways.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app