Genomes and Genes
Summary: A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.
- Pal J, Fulciniti M, Nanjappa P, Buon L, Tai Y, Tassone P, et al. Targeting PI3K and RAD51 in Barrett's adenocarcinoma: impact on DNA damage checkpoints, expression profile and tumor growth. Cancer Genomics Proteomics. 2012;9:55-66 pubmed..Simultaneous suppression of PI3K and RAD51, especially in cells with lower AKT expression, can significantly reduce their proliferative potential. ..
- Neri P, Ren L, Gratton K, Stebner E, Johnson J, Klimowicz A, et al. Bortezomib-induced "BRCAness" sensitizes multiple myeloma cells to PARP inhibitors. Blood. 2011;118:6368-79 pubmed publisher..Our studies indicate that bortezomib impairs HR in MM and results in a contextual synthetic lethality when combined with PARP inhibitors...
- Qing Y, Yamazoe M, Hirota K, Dejsuphong D, Sakai W, Yamamoto K, et al. The epistatic relationship between BRCA2 and the other RAD51 mediators in homologous recombination. PLoS Genet. 2011;7:e1002148 pubmed publisherb>RAD51 recombinase polymerizes at the site of double-strand breaks (DSBs) where it performs DSB repair. The loss of RAD51 causes extensive chromosomal breaks, leading to apoptosis...
- Kim T, Ko J, Hu L, Kim S, Bishop A, Vijg J, et al. RAD51 mutants cause replication defects and chromosomal instability. Mol Cell Biol. 2012;32:3663-80 pubmed publisher..We found very low levels of mutant protein present at these sites compared to normal protein, suggesting that low levels of mutant protein were sufficient for disruption of RAD51 activity and generation of chromosomal rearrangements...
- Grimme J, Spies M. FRET-based assays to monitor DNA binding and annealing by Rad52 recombination mediator protein. Methods Mol Biol. 2011;745:463-83 pubmed publisher..replication forks by facilitating replacement of ssDNA binding protein replication protein A (RPA) with Rad51 recombinase and by mediating annealing of two complementary DNA strands protected by RPA...
- Marini V, Krejci L. Unwinding of synthetic replication and recombination substrates by Srs2. DNA Repair (Amst). 2012;11:789-98 pubmed publisher..These biochemical results help us understand the possible role of Srs2 in the processing of stalled or blocked replication forks as a part of post-replication repair as well as homologous recombination (HR). ..
- Amunugama R, He Y, Willcox S, Forties R, Shim K, Bundschuh R, et al. RAD51 protein ATP cap regulates nucleoprotein filament stability. J Biol Chem. 2012;287:8724-36 pubmed publisher..These studies suggest that the HsRAD51(Asp-316) salt bridge may function as a conformational sensor that enhances turnover at the expense of recombinase activity...
- Busygina V, Saro D, Williams G, Leung W, Say A, Sehorn M, et al. Novel attributes of Hed1 affect dynamics and activity of the Rad51 presynaptic filament during meiotic recombination. J Biol Chem. 2012;287:1566-75 pubmed publisher..Our results shed light on the mechanism of action of Hed1 in meiotic recombination control. ..
- Endo M, Nakayama S, Umeda Hara C, Ohtsuki N, Saika H, Umeda M, et al. CDKB2 is involved in mitosis and DNA damage response in rice. Plant J. 2012;69:967-77 pubmed publisher..In addition, polyploid cells due to endomitosis were present in CDKB2;1 knockdown rice, suggesting an important role for Orysa;CDKB2;1 during mitosis...
- Crismani W, Portemer V, Froger N, Chelysheva L, Horlow C, Vrielynck N, et al. MCM8 is required for a pathway of meiotic double-strand break repair independent of DMC1 in Arabidopsis thaliana. PLoS Genet. 2013;9:e1003165 pubmed publisher..We propose that MCM8 is involved with RAD51 in a backup pathway that repairs meiotic DSB without giving CO when the major pathway, which relies on DMC1, fails. ..
- Atwell S, Disseau L, Stasiak A, Stasiak A, Renodon Cornière A, Takahashi M, et al. Probing Rad51-DNA interactions by changing DNA twist. Nucleic Acids Res. 2012;40:11769-76 pubmed publisher..Our observations permit a better understanding of the role of ATP hydrolysis in Rad51-mediated homologous pairing and strand exchange. ..
- Siaud N, Barbera M, Egashira A, Lam I, Christ N, Schlacher K, et al. Plasticity of BRCA2 function in homologous recombination: genetic interactions of the PALB2 and DNA binding domains. PLoS Genet. 2011;7:e1002409 pubmed publisher..Human BRCA2 is 3,418 amino acids and is comprised of multiple domains that interact with the RAD51 recombinase and other proteins as well as with DNA...
- Ochiai K, Yoshikawa Y, Yoshimatsu K, Oonuma T, Tomioka Y, Takeda E, et al. Valine 1532 of human BRC repeat 4 plays an important role in the interaction between BRCA2 and RAD51. FEBS Lett. 2011;585:1771-7 pubmed publisher..However, the cancer-associated V1532F mutant exhibited very weak interaction with RAD51. This study used a comparative analysis of BRC4 between animal species to identify V1532 as an important residue that interacts with RAD51. ..
- Suwaki N, Klare K, Tarsounas M. RAD51 paralogs: roles in DNA damage signalling, recombinational repair and tumorigenesis. Semin Cell Dev Biol. 2011;22:898-905 pubmed publisher..In addition, we highlight potential functional similarities with the BRCA2 tumour suppressor, through the recently reported links between RAD51 paralog deficiencies and tumorigenesis triggered by genome instability. ..
- Nimonkar A, Dombrowski C, Siino J, Stasiak A, Stasiak A, Kowalczykowski S. Saccharomyces cerevisiae Dmc1 and Rad51 proteins preferentially function with Tid1 and Rad54 proteins, respectively, to promote DNA strand invasion during genetic recombination. J Biol Chem. 2012;287:28727-37 pubmed publisher..Our data are consistent with the hypothesis that Rad51-Rad54 function together to promote intersister DNA strand exchange, whereas Dmc1-Tid1 tilt the bias toward interhomolog DNA strand exchange. ..
- Say A, Ledford L, Sharma D, Singh A, Leung W, Sehorn H, et al. The budding yeast Mei5-Sae3 complex interacts with Rad51 and preferentially binds a DNA fork structure. DNA Repair (Amst). 2011;10:586-94 pubmed publisher..We determined Mei5-Sae3 interacts with the Rad51 recombinase through the N-terminal domain of Mei5...
- Schlacher K, Wu H, Jasin M. A distinct replication fork protection pathway connects Fanconi anemia tumor suppressors to RAD51-BRCA1/2. Cancer Cell. 2012;22:106-16 pubmed publisher..Collective results imply a unified molecular mechanism for repair-independent functions of FA, RAD51, and BRCA1/2 proteins in preventing genomic instability and suppressing tumorigenesis. ..
- Karpenshif Y, Bernstein K. From yeast to mammals: recent advances in genetic control of homologous recombination. DNA Repair (Amst). 2012;11:781-8 pubmed publisher..In this review, we highlight potential candidates of Srs2 orthologues in human cells, and we discuss recent advances in understanding how Srs2's so-called "anti-recombinase" activity is regulated. ..
- Budke B, Kalin J, Pawlowski M, Zelivianskaia A, Wu M, Kozikowski A, et al. An optimized RAD51 inhibitor that disrupts homologous recombination without requiring Michael acceptor reactivity. J Med Chem. 2013;56:254-63 pubmed publisher..Like compound 1, compound 7a specifically inhibits HR repair in human cells. ..
- Cloud V, Chan Y, Grubb J, Budke B, Bishop D. Rad51 is an accessory factor for Dmc1-mediated joint molecule formation during meiosis. Science. 2012;337:1222-5 pubmed publisher..We further provide biochemical evidence that Rad51 acts with Mei5-Sae3 as a Dmc1 accessory factor. Thus, Rad51 is a multifunctional protein that catalyzes recombination directly in mitosis and indirectly, via Dmc1, during meiosis. ..
- Da Ines O, Degroote F, Amiard S, Goubely C, Gallego M, White C. Effects of XRCC2 and RAD51B mutations on somatic and meiotic recombination in Arabidopsis thaliana. Plant J. 2013;74:959-70 pubmed publisher..The roles of RAD51B and XRCC2 in recombination are thus not limited to mitotic cells. ..
- Jasin M, Rothstein R. Repair of strand breaks by homologous recombination. Cold Spring Harb Perspect Biol. 2013;5:a012740 pubmed publisher..We discuss the enzymology of the process, followed by studies on DSB repair in living cells. Whenever possible, we cite both original articles and reviews to aid the reader for further studies. ..
- Holloman W. Unraveling the mechanism of BRCA2 in homologous recombination. Nat Struct Mol Biol. 2011;18:748-54 pubmed publisher..This review highlights recent studies on BRCA2 and its orthologs that have begun to illuminate the molecular mechanisms by which these proteins control homologous recombination. ..
- Takaku M, Tsujita T, Horikoshi N, Takizawa Y, Qing Y, Hirota K, et al. Purification of the human SMN-GEMIN2 complex and assessment of its stimulation of RAD51-mediated DNA recombination reactions. Biochemistry. 2011;50:6797-805 pubmed publisher..These results provide the first evidence that the SMN-GEMIN2 complex plays a role in homologous recombination, in addition to spliceosomal snRNP assembly. ..
- Chi P, Kwon Y, Visnapuu M, Lam I, Santa Maria S, Zheng X, et al. Analyses of the yeast Rad51 recombinase A265V mutant reveal different in vivo roles of Swi2-like factors. Nucleic Acids Res. 2011;39:6511-22 pubmed publisher..Additionally, we show that a third Swi2-like factor, Uls1, contributes toward Rad51 clearance from chromatin in the absence of Rad54 and Rdh54, and define a hierarchy of action of the Swi2-like translocases for chromosome damage repair. ..
- Ceballos S, Heyer W. Functions of the Snf2/Swi2 family Rad54 motor protein in homologous recombination. Biochim Biophys Acta. 2011;1809:509-23 pubmed publisher..We will discuss how these results relate to in vivo functions of Rad54 during homologous recombination in somatic cells and during meiosis. This article is part of a Special Issue entitled: Snf2/Swi2 ATPase structure and function. ..
- Huang F, Motlekar N, Burgwin C, Napper A, Diamond S, Mazin A. Identification of specific inhibitors of human RAD51 recombinase using high-throughput screening. ACS Chem Biol. 2011;6:628-35 pubmed publisher..The described approach can be used for identification of specific inhibitors of other human proteins that play an important role in DNA repair, e.g., RAD54 or Bloom's syndrome helicase. ..
- Budke B, Logan H, Kalin J, Zelivianskaia A, Cameron McGuire W, Miller L, et al. RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells. Nucleic Acids Res. 2012;40:7347-57 pubmed publisher..Furthermore, RI-1 represents a unique tool to dissect the network of reaction pathways that contribute to DNA repair in cells. ..
- Falvo E, Strigari L, Citro G, Giordano C, Arcangeli S, Soriani A, et al. Dose and polymorphic genes xrcc1, xrcc3, gst play a role in the risk of articledeveloping erythema in breast cancer patients following single shot partial breast irradiation after conservative surgery. BMC Cancer. 2011;11:291 pubmed publisher
- Mitchel K, Lehner K, Jinks Robertson S. Heteroduplex DNA position defines the roles of the Sgs1, Srs2, and Mph1 helicases in promoting distinct recombination outcomes. PLoS Genet. 2013;9:e1003340 pubmed publisher..The hDNA data are consistent with the proposed role of Sgs1 in the dissolution of double HJs, and we propose that Srs2 dismantles nicked HJs. ..
- Flott S, Kwon Y, Pigli Y, Rice P, Sung P, Jackson S. Regulation of Rad51 function by phosphorylation. EMBO Rep. 2011;12:833-9 pubmed publisher..These data suggest a model in which Mec1-mediated phosphorylation of Rad51 Ser 192 in response to DNA damage controls Rad51 activity and DNA repair by homologous recombination. ..
- Bernstein K, Reid R, Sunjevaric I, Demuth K, Burgess R, Rothstein R. The Shu complex, which contains Rad51 paralogues, promotes DNA repair through inhibition of the Srs2 anti-recombinase. Mol Biol Cell. 2011;22:1599-607 pubmed publisher..We propose that the Shu complex shifts the balance of repair toward Rad51 filament stabilization by inhibiting the disassembly reaction of Srs2. ..
- Kurzbauer M, Uanschou C, Chen D, Schlögelhofer P. The recombinases DMC1 and RAD51 are functionally and spatially separated during meiosis in Arabidopsis. Plant Cell. 2012;24:2058-70 pubmed publisher..Taken together, these results demonstrate that DMC1 functions independently and spatially separated from RAD51 during meiosis and that ATR is an integral part of the regular meiotic program. ..
- Nakamura K, Kato A, Kobayashi J, Yanagihara H, Sakamoto S, Oliveira D, et al. Regulation of homologous recombination by RNF20-dependent H2B ubiquitination. Mol Cell. 2011;41:515-28 pubmed publisher..Finally, the function of RNF20 in HRR can be partially bypassed by forced chromatin relaxation. Thus, the RNF20-mediated H2B ubiquitination at DSBs plays a critical role in HRR through chromatin remodeling. ..
- Kokabu Y, Murayama Y, Kuwabara N, Oroguchi T, Hashimoto H, Tsutsui Y, et al. Fission yeast Swi5-Sfr1 protein complex, an activator of Rad51 recombinase, forms an extremely elongated dogleg-shaped structure. J Biol Chem. 2011;286:43569-76 pubmed publisher..We propose a model for how the Swi5-Sfr1 complex binds to the Rad51 filament, in which the Swi5-Sfr1 complex fits into the groove of the Rad51 filament, leading to an active and stable presynaptic filament. ..
- Cole F, Kauppi L, Lange J, Roig I, Wang R, Keeney S, et al. Homeostatic control of recombination is implemented progressively in mouse meiosis. Nat Cell Biol. 2012;14:424-30 pubmed publisher..Meiotic recombination exemplifies how order can be progressively implemented in a self-organizing system despite natural cell-to-cell disparities in the underlying biochemical processes...
- Santa Maria S, Kwon Y, Sung P, Klein H. Characterization of the interaction between the Saccharomyces cerevisiae Rad51 recombinase and the DNA translocase Rdh54. J Biol Chem. 2013;288:21999-2005 pubmed publisher..Altogether, these results reveal a distinction between damage sensitivity and Rad51 removal with regard to Rdh54 interaction with Rad51...
- Oganesian L, Karlseder J. Mammalian 5' C-rich telomeric overhangs are a mark of recombination-dependent telomere maintenance. Mol Cell. 2011;42:224-36 pubmed publisher..Transient siRNA-based depletion of the HR-specific proteins RAD51, RAD52, and XRCC3 resulted in changes in C-overhang levels, implicating the involvement of 5'-C-overhangs in the HR-dependent pathway of telomere maintenance. ..
- Chen H, Ma Z, VanderWaal R, Feng Z, Gonzalez Suarez I, Wang S, et al. The mTOR inhibitor rapamycin suppresses DNA double-strand break repair. Radiat Res. 2011;175:214-24 pubmed..Thus our results show that radiosensitization by mTOR inhibitors occurs via disruption of the major two DNA DSB repair pathways. ..
- Bergink S, Ammon T, Kern M, Schermelleh L, Leonhardt H, Jentsch S. Role of Cdc48/p97 as a SUMO-targeted segregase curbing Rad51-Rad52 interaction. Nat Cell Biol. 2013;15:526-32 pubmed publisher..Cdc48 associates with SUMOylated Rad52, a factor that assembles the Rad51 recombinase on chromatin...
- Meneely P, McGovern O, Heinis F, Yanowitz J. Crossover distribution and frequency are regulated by him-5 in Caenorhabditis elegans. Genetics. 2012;190:1251-66 pubmed publisher..The localization of HIM-5 to the autosomes depends on the activities of both xnd-1 and him-17 allowing us to begin to establish pathways for the control of crossover distribution and frequency. ..
- Chen J, Zhu F, Weaks R, Biswas A, Guo R, Li Y, et al. E2F1 promotes the recruitment of DNA repair factors to sites of DNA double-strand breaks. Cell Cycle. 2011;10:1287-94 pubmed publisher..These findings establish new roles for E2F1 in the DNA damage response, which may directly contribute to DNA repair and genome maintenance. ..
- Bosaeus N, El Sagheer A, Brown T, Smith S, Akerman B, Bustamante C, et al. Tension induces a base-paired overstretched DNA conformation. Proc Natl Acad Sci U S A. 2012;109:15179-84 pubmed..The extension observed in the reversible transition coincides with that produced on DNA by binding of bacterial RecA and human Rad51, pointing to its possible relevance in homologous recombination. ..
- Tsai S, Su G, Lin S, Chung C, Xue X, Dunlop M, et al. Rad51 presynaptic filament stabilization function of the mouse Swi5-Sfr1 heterodimeric complex. Nucleic Acids Res. 2012;40:6558-69 pubmed publisher..The DNA strand invasion reaction in HR is mediated by a helical filament of the Rad51 recombinase assembled on single-stranded DNA that is derived from the nucleolytic processing of the primary lesion...
- Sirbu B, Lachmayer S, Wülfing V, Marten L, Clarkson K, Lee L, et al. ATR-p53 restricts homologous recombination in response to replicative stress but does not limit DNA interstrand crosslink repair in lung cancer cells. PLoS ONE. 2011;6:e23053 pubmed publisher..Here, we show for the first time that p53 downregulates foci formation of the RAD51 recombinase in response to replicative stress in H1299 lung cancer cells in a manner that is independent of its role as ..
- Huang F, Mazina O, Zentner I, Cocklin S, Mazin A. Inhibition of homologous recombination in human cells by targeting RAD51 recombinase. J Med Chem. 2012;55:3011-20 pubmed publisher..We propose to use 1 for analysis of cellular functions of RAD51. Because DSB- and ICL-inducing agents are commonly used in anticancer therapy, specific inhibitors of RAD51 may also help to increase killing of cancer cells. ..
- Moldovan G, Dejsuphong D, Petalcorin M, Hofmann K, Takeda S, Boulton S, et al. Inhibition of homologous recombination by the PCNA-interacting protein PARI. Mol Cell. 2012;45:75-86 pubmed publisher..Thus, we propose that PARI is a long sought-after factor that suppresses inappropriate recombination events at mammalian replication forks...
- Islam M, Paquet N, Fox D, Dray E, Zheng X, Klein H, et al. A variant of the breast cancer type 2 susceptibility protein (BRC) repeat is essential for the RECQL5 helicase to interact with RAD51 recombinase for genome stabilization. J Biol Chem. 2012;287:23808-18 pubmed publisher..breast cancer type 2 susceptibility protein), which promotes homologous recombination (HR) by regulating RAD51 recombinase activity...
- Fornander L, Frykholm K, Reymer A, Renodon Cornière A, Takahashi M, Norden B. Ca2+ improves organization of single-stranded DNA bases in human Rad51 filament, explaining stimulatory effect on gene recombination. Nucleic Acids Res. 2012;40:4904-13 pubmed publisher..It is proposed that the larger Ca(2+) stabilizes the loop conformation and thereby the protein-DNA interaction. A tight binding of DNA, with bases perpendicularly oriented, could facilitate strand exchange. ..