Homologous-pairing activity of the human DNA-repair proteins Xrcc3⋅Rad51C

Kurumizaka, Hitoshi; Ikawa, Shiro; Nakada, Maki; Eda, Keiko; Kagawa, Wataru; Takata, Minoru; Takeda, Shunichi; Yokoyama, Shigeyuki; Shibata, Takehiko

doi:10.1073/pnas.091603098

Cited by 122 publications

(116 citation statements)

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“…Although the homologous pairing activity of the human RAD51 protein alone is too weak to be detected by the D-loop formation assay (31,32), mTPBIP/HOP2 did not enhance the RAD51-mediated D-loop formation to a detectable level (Fig. 3C).…”

Section: Tbpip/hop2 Enhances the Dmc1-mediated Homologous Pairingmentioning

confidence: 99%

“…The 5Ј ends of the oligonucleotides were labeled with T4 polynucleotide kinase (New England Biolabs) in the presence of [␥- 32 …”

Section: Overexpression and Purification Of The Mouse And Human Tbpipmentioning

confidence: 99%

“…The protein concentrations used in the experiments were 0 M (lanes 1, 5, 9, 13, 17, 21, 25, 29, and 33), 2 M (lanes 2, 6, 10, 14, 18, 22, 26, 30, and 34), 4 M (lanes 3, 7, 11, 15, 19, 23, 27, 31, and 35), and 8 M (lanes 4, 8, 12, 16, 20, 24, 28, 32, and 36). [6][7][8][10][11][12][14][15][16][18][19][20][22][23][24][26][27][28][30][31][32][34][35][36] (Ref. 36 and Fig.…”

Section: Tbpip/hop2 Enhances the Dmc1-mediated Homologous Pairingmentioning

confidence: 99%

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Positive Role of the Mammalian TBPIP/HOP2 Protein in DMC1-mediated Homologous Pairing

Enomoto¹,

Kinebuchi²,

Sato

et al. 2004

Journal of Biological Chemistry

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In meiosis, homologous recombination preferentially occurs between homologous chromosomes rather than between sister chromatids, which is opposite to the bias of mitotic recombinational repair. The TBPIP/HOP2 protein is a factor that ensures the proper pairing of homologous chromosomes during meiosis. In the present study, we found that the purified mouse TBPIP/ HOP2 protein stimulated homologous pairing catalyzed by the meiotic DMC1 recombinase in vitro. In contrast, TBPIP/HOP2 did not stimulate homologous pairing by RAD51, which is another homologous pairing protein acting in both meiotic and mitotic recombination. The positive effect of TBPIP/HOP2 in the DMC1-mediated homologous pairing was only observed when TBPIP/ HOP2 first binds to double-stranded DNA, not to singlestranded DNA, before the initiation of the homologous pairing reaction. Deletion analyses revealed that the C-terminal basic region of TBPIP/HOP2 is required for efficient DNA binding and is also essential for its homologous pairing stimulation activity. Therefore, these results suggest that TBPIP/HOP2 directly binds to DNA and functions as an activator for DMC1 during the homologous pairing step in meiosis.During meiosis, two successive rounds of nuclear division, meiosis I and meiosis II, are promoted with a single round of DNA replication. As a result, diploid cells produce haploid gametes in eukaryotes. In the cell division at meiosis I, homologous chromosomes are aligned, and a high level of recombination occurs between homologous chromosomes but not between sister chromatids. This preferential recombination between homologous chromosomes, called homologous recombination, ensures their correct segregation at meiosis I through the formation of chiasmata, which physically connect homologous chromosomes.Homologous recombination is initiated by double strand break (DSB) 1 formation by SPO11 at the initiation sites for recombination (1-3). Then a single-stranded DNA (ssDNA) tail derived from a DSB site invades the homologous doublestranded DNA (dsDNA) to form a heteroduplex. This strand invasion step, called homologous pairing, is the key step in homologous recombination. In Escherichia coli, the RecA protein catalyzes the homologous pairing step (4, 5). Two eukaryotic homologues of RecA, the RAD51 and DMC1 proteins, which are conserved from yeast to human, have been identified (6 -9) and have been shown to catalyze homologous pairing in vitro (10 -15). The RAD51 gene is expressed in both mitotic and meiotic cells, but the DMC1 gene functions only in meiotic cells. Disruption of the Rad51 gene results in early embryonic lethality in mice (16,17). In chicken DT40 cells, the RAD51 gene disruption causes the accumulation of spontaneous chromosomal breaks and significantly reduces the recombination frequency between sister chromatids (18,19). In contrast, disruption of the Dmc1 gene does not cause lethality in mice, but the dmc1 knock-out mice are sterile with an arrest of gametogenesis in the first meiotic prophase (20,21). Therefore, DMC1 is a me...

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Section: Tbpip/hop2 Enhances the Dmc1-mediated Homologous Pairingmentioning

confidence: 99%

“…The 5Ј ends of the oligonucleotides were labeled with T4 polynucleotide kinase (New England Biolabs) in the presence of [␥- 32 …”

Section: Overexpression and Purification Of The Mouse And Human Tbpipmentioning

confidence: 99%

Section: Tbpip/hop2 Enhances the Dmc1-mediated Homologous Pairingmentioning

confidence: 99%

See 1 more Smart Citation

Positive Role of the Mammalian TBPIP/HOP2 Protein in DMC1-mediated Homologous Pairing

Enomoto¹,

Kinebuchi²,

Sato

et al. 2004

Journal of Biological Chemistry

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“…[7][8][9][10] Cell lines lacking RAD51 or its paralogs (for example, XRCC3) demonstrate increased sensitivity to DNA damaging agents like ionizing radiation. [11][12][13] In addition, RAD51 deficient cell lines show an increased frequency of spontaneous chromosomal aberrations contributing to genetic instability. 14 These data suggest that RAD51 as well as XRCC3 play an important role in maintaining genomic stability.…”

Section: Introductionmentioning

confidence: 99%

DNA repair polymorphisms and outcome of chemotherapy for acute myelogenous leukemia: a report from the Children's Oncology Group

et al. 2007

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Polymorphisms of DNA repair genes RAD51 and XRCC3 increase susceptibility to acute myeloid leukemia (AML) in adults, an effect enhanced by deletion of the glutathione-Stransferase M1 (GSTM1) gene. In this study, we genotyped 452 children with de novo AML treated on CCG protocols 2941 and 2961 and compared genotype frequencies with those of normal blood donors, and analyzed the impact of genotype on outcome of therapy. XRCC3 Thr241Met, RAD51 G135C and GSTM1 genotypes did not increase susceptibility to AML when assessed singly. In contrast, when XRCC3 and RAD51 genotypes were examined together a significant increase in susceptibility to AML was seen in children with variant alleles. Analysis of outcome of therapy showed that patients heterozygous for the XRCC3 Thr241Met allele had improved postinduction disease-free survival compared to children homozygous for the major or minor allele, each of whom had similar outcomes. Improved survival was due to reduced relapse in the heterozygous children, and this effect was most marked in children randomized to therapy likely to generate DNA doublestrand breaks (etoposide, daunomycin), compared with antimetabolite (fludarabine, cytarabine) based therapy. In contrast, RAD51 G135C and the GSTM1 deletion polymorphism did not influence outcome of AML therapy in our study population.

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“…These results together with the observations that RAD51B [107,108], RAD51C [111], RAD51D [117], and XRCC2 [123] are required for proper formation of RAD51 foci, indicate that these proteins may function as a complex both in assembling the RAD51 complex and in the initial processing of the single-stranded DNA at the damaged sites. Another complex, with RAD51C and XRCC3, was originally detected with a yeast two-hybrid system and then with interaction of proteins expressed in baculovirusinfected insect cells [132][133][134], and then confirmed with human cells lines that express isotope-tagged XRCC3 or RAD51C proteins [135]. In addition, XRCC3 is shown to be required for stabilizing RAD51C possibly by forming dimers, and this function requires the ATPase activity, suggesting that XRCC3 may regulate the dimerization through its ATP binding and hydrolysis activity [136].…”

Section: Rad51 Paralogs In Animals and Plants: Rad51b Rad51c Rad51dmentioning

confidence: 99%

Double-stranded DNA breaks and gene functions in recombination and meiosis

Mā

2006

Cell Res

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Gene functions in recombination and meiosis 402 npg REVIEW Meiotic prophase I is a long and complex phase. Homologous recombination is an important process that occurs between homologous chromosomes during meiotic prophase I. Formation of chiasmata, which hold homologous chromosomes together until the metaphase I to anaphase I transition, is critical for proper chromosome segregation. Recent studies have suggested that the SPO11 proteins have conserved functions in a number of organisms in generating sites of double-stranded DNA breaks (DSBs) that are thought to be the starting points of homologous recombination. Processing of these sites of DSBs requires the function of RecA homologs, such as RAD51, DMC1, and others, as suggested by mutant studies; thus the failure to repair these meiotic DSBs results in abnormal chromosomal alternations, leading to disrupted meiosis. Recent discoveries on the functions of these RecA homologs have improved the understanding of the mechanisms underlying meiotic homologous recombination.Cell Research (2006) Meiosis is a highly coordinated cell division, which generates four haploid reproductive cells required for sexual reproduction. Meiosis involves one round of DNA replication and two nuclear divisions, meiosis I and meiosis II. The first nuclear division leads to the segregation of homologous chromosomes (homologs), and is unique to meiosis. During the second division, sister chromatids are separated, resulting in the formation of four haploid nuclei and followed by the meiotic cytokinesis that forms four haploid cells. Similar to mitosis, both meiosis I and meiosis II can be divided into four stages: prophase, metaphase, anaphase, and telophase.However, meiosis I differs from meiosis II as meiosis I involves homology search, pairing, interhomolog recombination, and synapsis of homologs, processes that are required for correct association and segregation of homologs. The prophase stage of meiosis I, or prophase I, has been the target of interest because of the occurrence of these major processes of chromosome interactions. During early prophase I, arms of sister chromosomes are closely associated by protein complexes called cohesins, which are removed during the metaphase I/anaphase I transition. However, the centromere regions remained associated until the segregation of sister chromatids during meiosis II. Homologous pairing is the result of interaction between homologous chromosomes relying on the homology of DNA sequences [1,2], and is considered to be a transient and non-stable association between homologous chromosomes. Pairing between homologous chromosomes facilitates the process of recombination. The recombination process confers the interexchange of genetic information between non-sister chromatids, and generates chiasmata, which ensure proper association between homologous chromosomes prior to chromosome segregation at anaphase I. Synapsis, however, is a stable association by forming synaptonemal complexes between chromosomes. Synaptonemal complexes are threeparti...

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Homologous-pairing activity of the human DNA-repair proteins Xrcc3⋅Rad51C

Cited by 122 publications

References 45 publications

Positive Role of the Mammalian TBPIP/HOP2 Protein in DMC1-mediated Homologous Pairing

Positive Role of the Mammalian TBPIP/HOP2 Protein in DMC1-mediated Homologous Pairing

DNA repair polymorphisms and outcome of chemotherapy for acute myelogenous leukemia: a report from the Children's Oncology Group

Double-stranded DNA breaks and gene functions in recombination and meiosis

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