Recombinational repair in yeast: functional interactions between Rad51 and Rad54 proteins

Clever, Beate; Interthal, Heidrun; Schmuckli‐Maurer, Jacqueline; King, Jaime S.; Sigrist, Markus W.; Heyer, Wolf Dietrich

doi:10.1093/emboj/16.9.2535

Cited by 167 publications

(123 citation statements)

References 82 publications

Supporting

Mentioning

112

Contrasting

Order By: Relevance

“…Experiments using the yeast two-hybrid system and immunoprecipitation proved that Rad51 protein can interact with Rad54 protein (41,42). We demonstrated directly that Rad51 protein retains its ability to interact with Rad54 protein when it is assembled into a filament on DNA, and we also showed that Rad54 protein also interacts with the DNA component of the complex (Fig.…”

Section: Discussionsupporting

confidence: 53%

“…For instance, the Rad51 protein interacts with a number of other homologous recombination proteins, including Rad52 protein (8), Rad55 protein (40), and Rad54 protein (41,42). In addition, Rad55 protein forms a stable heterodimer with Rad57 protein (21); Rad50 protein, Mre11 protein, and Xrs2 protein form a heterotrimer (43); and Rad52 protein interacts with RPA (44,45).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A Novel Function of Rad54 Protein

Mazin¹,

Alexeev²,

Kowalczykowski³

2003

Journal of Biological Chemistry

158

View full text Add to dashboard Cite

Homologous recombination is important for the repair of double-stranded DNA breaks in all organisms. Rad51 and Rad54 proteins are two key components of the homologous recombination machinery in eukaryotes. In vitro, Rad51 protein assembles with singlestranded DNA to form the helical nucleoprotein filament that promotes DNA strand exchange, a basic step of homologous recombination. Rad54 protein interacts with this Rad51 nucleoprotein filament and stimulates its DNA pairing activity, suggesting that Rad54 protein is a component of the nucleoprotein complex involved in the DNA homology search. Here, using physical criteria, we demonstrate directly the formation of Rad54-Rad51-DNA nucleoprotein co-complexes that contain equimolar amounts of each protein. The binding of Rad54 protein significantly stabilizes the Rad51 nucleoprotein filament formed on either single-stranded DNA or double-stranded DNA. The Rad54-stabilized nucleoprotein filament is more competent in DNA strand exchange and acts over a broader range of solution conditions. Thus, the co-assembly of an interacting partner with the Rad51 nucleoprotein filament represents a novel means of stabilizing the biochemical entity central to homologous recombination, and reveals a new function of Rad54 protein.Homologous recombination plays an essential role in repair of DNA double-stranded breaks, a lethal type of DNA damage. The mechanisms of double-stranded break repair by recombination have been extensively investigated at the genetic and biochemical levels (1-6). In yeast, genetic analysis reveals a set of genes, called the RAD52 epistasis group, that are directly involved in double-stranded break repair (7). This group includes the RAD50, RAD58/MRE11, XRS2, RPA1, RAD51, RAD52, RAD54, RAD55, RAD57, and RAD59 genes. Among the proteins encoded by these genes, the Rad51 protein is the most evolutionarily conserved; its homologues are spread from bacteria to mammals (8). The Rad51 protein family members possess a unique property; they form helical nucleoprotein filaments with DNA (9 -11) and promote DNA pairing and strand transfer, a basic step of homologous recombination (11-16).More recently, it was demonstrated that Rad52 protein, Rad54 protein, and the Rad55/Rad57 heterodimer stimulate DNA pairing promoted by Rad51 protein. The mechanistic studies revealed that stimulation by Rad52 protein and the Rad55/Rad57 proteins is at the early (presynaptic) stage of DNA strand exchange. Rad52 protein enhances the ability of Rad51 protein to displace RPA from ssDNA 1 (17)(18)(19)(20), as do the Rad55/Rad57 proteins, but by a different mechanism (21).The mechanism by which Rad54 protein stimulates the DNA pairing activity of Rad51 protein is different (22-28). It was found that, in contrast to other proteins that stimulate the DNA pairing activity of Rad51 protein, Rad54 protein acts at a later (synaptic) stage of DNA strand exchange (24, 29). Rad54 protein belongs to the Snf2/Swi2 group of proteins, which are involved in ATP-dependent remodeling of protein complexes, in...

show abstract

Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

A Novel Function of Rad54 Protein

Mazin¹,

Alexeev²,

Kowalczykowski³

2003

Journal of Biological Chemistry

158

View full text Add to dashboard Cite

show abstract

“…Increased expression of Huntingtin in anaplastic tumors might have led to inhibition of apoptosis and induction of BDNF and/or TrkB in the tumors. Reduced homologous recombination and ionizing radiation or X-ray resistance have been observed in RAD54 deficiency yeast, Drosophila, chick cells and mice (Bezzubova et al, 1997;Clever et al, 1997;Essers et al, 1997;Kooistra et al, 1997Kooistra et al, , 1999. Elevation of hRAD54 expression in anaplastic tumors may also contribute to their therapy resistant phenotype.…”

Section: An Expression Signature For Anaplastic Wilms Tumormentioning

confidence: 99%

Transcript profiling of Wilms tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia

Kessler

Williams

2004

Oncogene

View full text Add to dashboard Cite

Anaplasia (unfavorable histology) is associated with therapy resistance and poor prognosis of Wilms tumor, but the molecular basis for this phenotype is unclear. Here, we used a cDNA array with 9240 clones relevant to cancer biology and/or kidney development to examine the expression profiles of 54 Wilms tumors, five normal kidneys and fetal kidney. By linking genes differentially expressed between fetal kidney and Wilms tumors to kidney morphogenesis, we found that genes expressed at a higher level in Wilms tumors tend to be expressed more in uninduced metanephrogenic mesenchyme or blastema than in their differentiated structures. Conversely, genes expressed at a lower level in Wilms tumors tend to be expressed less in uninduced metanephrogenic mesenchyme or blastema. We also identified 97 clones representing 76 Unigenes or unclustered ESTs that clearly separate anaplastic Wilms tumors from tumors with favorable histology. Genes in this set provide insight into the nature of the abnormal nuclear morphology of anaplastic tumors and may facilitate identification of molecular targets to improve their responsiveness to treatment.

show abstract

“…Rad54 protein physically interacts with Rad51 [7,25,26] and greatly enhances the ability of Rad51 to form DNA joints [7]. The promotion of Rad51-mediated homologous DNA pairing and strand exchange by Rad54 requires the ATPase activity of the latter and physical interaction between these two HR factors [27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Synergistic action of the Saccharomyces cerevisiae homologous recombination factors Rad54 and Rad51 in chromatin remodeling

et al. 2007

View full text Add to dashboard Cite

Rad54, a member of the Swi2/Snf2 protein family, works in concert with the RecA-like recombinase Rad51 during the early and late stages of homologous recombination. Rad51 markedly enhances the activities of Rad54, including the induction of topological changes in DNA and the remodeling of chromatin structure. Reciprocally, Rad54 promotes Rad51-mediated DNA strand invasion with either naked or chromatinized DNA. Here, using various Saccharomyces cerevisiae rad51 and rad54 mutant proteins, mechanistic aspects of Rad54/Rad51-mediated chromatin remodeling are defined. Disruption of the Rad51-Rad54 complex leads to a marked attenuation of chromatin remodeling activity. Moreover, we present evidence that assembly of the Rad51 presynaptic filament represents an obligatory step in the enhancement of the chromatin remodeling reaction. Interestingly, we find a specific interaction of the N-terminal tail of histone H3 with Rad54 and show that the H3 tail interaction domain resides within the amino terminus of Rad54. These results suggest that Rad54-mediated chromatin remodeling coincides with DNA homology search by the Rad51 presynaptic filament and that this process is facilitated by an interaction of Rad54 with histone H3.

show abstract

Recombinational repair in yeast: functional interactions between Rad51 and Rad54 proteins

Cited by 167 publications

References 82 publications

A Novel Function of Rad54 Protein

A Novel Function of Rad54 Protein

Transcript profiling of Wilms tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia

Synergistic action of the Saccharomyces cerevisiae homologous recombination factors Rad54 and Rad51 in chromatin remodeling

Contact Info

Product

Resources

About