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Title: Suppression of mutagenesis by Rad51D-mediated homologous recombination

Abstract

Homologous recombinational repair (HRR) restores chromatid breaks arising during DNA replication and prevents chromosomal rearrangements that can occur from the misrepair of such breaks. In vertebrates, five Rad51 paralogs are identified that contribute in a nonessential but critical manner to HRR efficiency. We constructed and characterized a Rad51D knockout cell line in widely studied CHO cells. The rad51d mutant (51D1) displays sensitivity to a wide spectrum of induced DNA damage, indicating the broad relevance of HRR to genotoxicity. Untreated 51D1 cells exhibit {approx}5-fold elevated chromosomal breaks, a 12-fold increased rate of hprt mutation, and 4- to 10-fold increased rates of gene amplification at the dhfr and CAD loci, respectively. These results explicitly show the quantitative importance of HHR in preventing these types genetic alterations, which are associated with carcinogenesis. Thus, HRR copes in an error-free manner with spontaneous DNA damage encountered during DNA replication, and Rad51D is essential for this fidelity.

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
888609
Report Number(s):
UCRL-JRNL-217120
Journal ID: ISSN 0305-1048; NARHAD; TRN: US200618%%440
DOE Contract Number:  
W-7405-ENG-48
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nucleic Acids Research; Journal Volume: 34; Journal Issue: 5
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CARCINOGENESIS; CHO CELLS; CHROMATIDS; DNA DAMAGES; DNA REPLICATION; EFFICIENCY; GENE AMPLIFICATION; GENETICS; MUTAGENESIS; MUTANTS; RECOMBINATION; REPAIR; SENSITIVITY; VERTEBRATES

Citation Formats

Hinz, J M, Tebbs, R S, Wilson, P F, Nham, P B, Salazar, E P, Nagasawa, H, Urbin, S S, and Thompson, L H. Suppression of mutagenesis by Rad51D-mediated homologous recombination. United States: N. p., 2005. Web.
Hinz, J M, Tebbs, R S, Wilson, P F, Nham, P B, Salazar, E P, Nagasawa, H, Urbin, S S, & Thompson, L H. Suppression of mutagenesis by Rad51D-mediated homologous recombination. United States.
Hinz, J M, Tebbs, R S, Wilson, P F, Nham, P B, Salazar, E P, Nagasawa, H, Urbin, S S, and Thompson, L H. Tue . "Suppression of mutagenesis by Rad51D-mediated homologous recombination". United States. doi:. https://www.osti.gov/servlets/purl/888609.
@article{osti_888609,
title = {Suppression of mutagenesis by Rad51D-mediated homologous recombination},
author = {Hinz, J M and Tebbs, R S and Wilson, P F and Nham, P B and Salazar, E P and Nagasawa, H and Urbin, S S and Thompson, L H},
abstractNote = {Homologous recombinational repair (HRR) restores chromatid breaks arising during DNA replication and prevents chromosomal rearrangements that can occur from the misrepair of such breaks. In vertebrates, five Rad51 paralogs are identified that contribute in a nonessential but critical manner to HRR efficiency. We constructed and characterized a Rad51D knockout cell line in widely studied CHO cells. The rad51d mutant (51D1) displays sensitivity to a wide spectrum of induced DNA damage, indicating the broad relevance of HRR to genotoxicity. Untreated 51D1 cells exhibit {approx}5-fold elevated chromosomal breaks, a 12-fold increased rate of hprt mutation, and 4- to 10-fold increased rates of gene amplification at the dhfr and CAD loci, respectively. These results explicitly show the quantitative importance of HHR in preventing these types genetic alterations, which are associated with carcinogenesis. Thus, HRR copes in an error-free manner with spontaneous DNA damage encountered during DNA replication, and Rad51D is essential for this fidelity.},
doi = {},
journal = {Nucleic Acids Research},
number = 5,
volume = 34,
place = {United States},
year = {Tue Nov 15 00:00:00 EST 2005},
month = {Tue Nov 15 00:00:00 EST 2005}
}