1998
DOI: 10.1128/mcb.18.11.6430
|View full text |Cite
|
Sign up to set email alerts
|

Homologous Recombination, but Not DNA Repair, Is Reduced in Vertebrate Cells Deficient in RAD52

Abstract: Rad52 plays a pivotal role in double-strand break (DSB) repair and genetic recombination in Saccharomyces cerevisiae, where mutation of this gene leads to extreme X-ray sensitivity and defective recombination. Yeast Rad51 and Rad52 interact, as do their human homologues, which stimulates Rad51-mediated DNA strand exchange in vitro, suggesting that Rad51 and Rad52 act cooperatively. To define the role of Rad52 in vertebrates, we generated RAD52 ؊/؊ mutants of the chicken B-cell line DT40. Surprisingly, RAD52 ؊/… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

6
142
1

Year Published

1999
1999
2021
2021

Publication Types

Select...
6
2

Relationship

2
6

Authors

Journals

citations
Cited by 214 publications
(149 citation statements)
references
References 33 publications
6
142
1
Order By: Relevance
“…First, rejoining of DNA DSBs proceeds in DT40 cells with kinetics and overall characteristics similar to those of cells of human or rodent origin, despite the 1000-fold increase in their potential for HR (Buerstedde and Takeda, 1991). Second, rejoining of DNA DSBs occurs with wild-type kinetics in mutants generated by targeted disruption of genes critical for HR such as RAD51, RAD51B, RAD52 and RAD54, and despite the fact that gene targeting e ciency in these mutants is signi®cantly reduced Takata et al, , 2000Yamaguchi-Iwai et al, 1998). Third, rejoining of DNA DSBs follows similar half times in KU70 7/7 cells and the double mutant KU70 7/7 / RAD54 7/7 , suggesting that even on a genetic background that compromises NHEJ , disruption of an HR gene leaves practically unchanged fundamental characteristics of DNA DSB rejoining, such as repair half times.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…First, rejoining of DNA DSBs proceeds in DT40 cells with kinetics and overall characteristics similar to those of cells of human or rodent origin, despite the 1000-fold increase in their potential for HR (Buerstedde and Takeda, 1991). Second, rejoining of DNA DSBs occurs with wild-type kinetics in mutants generated by targeted disruption of genes critical for HR such as RAD51, RAD51B, RAD52 and RAD54, and despite the fact that gene targeting e ciency in these mutants is signi®cantly reduced Takata et al, , 2000Yamaguchi-Iwai et al, 1998). Third, rejoining of DNA DSBs follows similar half times in KU70 7/7 cells and the double mutant KU70 7/7 / RAD54 7/7 , suggesting that even on a genetic background that compromises NHEJ , disruption of an HR gene leaves practically unchanged fundamental characteristics of DNA DSB rejoining, such as repair half times.…”
Section: Discussionmentioning
confidence: 99%
“…This increase in HRR allows the generation of mutants by gene targeting with ease comparable to that of yeast and an evaluation of the role of HRR in DNA DSB rejoining. Although we have recently reported on various aspects of the radiation response for several DT40 mutants generated by targeted disruption of homologues of the RAD52 family of genes (Bezzubova et al, 1993;Sonoda et al, 1998;Takata et al, 1998Takata et al, , 2000Yamaguchi-Iwai et al, 1998), studies on DNA DSBs rejoining have not been reported to date.…”
Section: Introductionmentioning
confidence: 99%
“…Thus gene targeting was shown to be impaired in both mouse ES cells and in chicken B cells if RAD54 gene expression was eliminated 25,26 and to a lesser extent, if RAD52 was inactivated. 27,28 Equivalent experiments with RAD51 have not been possible because of the lethal effects of inactivation. 29 Resistance to DNA damage, presumably reflecting DNA repair by homologous recombination, is also severely reduced upon RAD54 or RAD51 inactivation.…”
Section: Correspondence: Acg Porter This Paper Is Dedicated To the Mementioning
confidence: 99%
“…Although more profound increases in efficiency will be required for therapeutic gene targeting, our data establish the important principle that the recombination machinery can be manipulated to promote gene targeting in human cells. Given the established involvement of RAD52 and RAD54 in gene targeting in vertebrate cells, [25][26][27][28] further manipulations of RAD gene expression with the aim of increasing the frequency of gene targeting are now an attractive proposition. A potential drawback of increasing gene targeting by enhancing homologous recombination activity is a possible concomitant increase in genome instability.…”
Section: Figure 4 Survival Of Hrad51 Overexpressing Cells To Ionisingmentioning
confidence: 99%
“…Rad54 protein is shown to interact with and stabilize the Rad51 nucleoprotein filament, stimulating its DNA pairing activity (9, 10). Interestingly, although Rad52 protein plays a pivotal role in DSB repair in Saccharomyces cerevisiae, the role of vertebrate and Schizosaccharomyces pombe Rad52 is much less significant (11)(12)(13).…”
mentioning
confidence: 99%