The Rad51 Paralog Rad51B Promotes Homologous Recombinational Repair

Takata, Minoru; Sasaki, Masao S.; Sonoda, Eiichiro; Fukushima, Toru; Morrison, Ciarán; Albala, Joanna S.; Swagemakers, Sigrid; Kanaar, Roland; Thompson, Larry H.; Takeda, Shunichi

doi:10.1128/mcb.20.17.6476-6482.2000

Cited by 243 publications

(207 citation statements)

References 67 publications

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“…In this regard, HR seems to repair this type of DNA damage efficiently during S to G2 phase. Indeed, hypersensitivity to cross-linking reagents is a consistent feature of HR repair in deficient mutants described in vertebrate cell lines (Liu et al, 1998;Takata et al, 2000;Sasaki et al, 2004). Furthermore, a recent study reported that the Arabidopsis mutant with impaired Xrcc3, which is the interaction partner of AtRad51C (Osakabe et al, 2002), also shows hypersensitivity to the cross-linking reagent .…”

Section: Discussionmentioning

confidence: 99%

Arabidopsis RAD51C Gene Is Important for Homologous Recombination in Meiosis and Mitosis

et al. 2005

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Rad51 is a homolog of the bacterial RecA recombinase, and a key factor in homologous recombination in eukaryotes. Rad51 paralogs have been identified from yeast to vertebrates. Rad51 paralogs are thought to play an important role in the assembly or stabilization of Rad51 that promotes homologous pairing and strand exchange reactions. We previously characterized two RAD51 paralogous genes in Arabidopsis (Arabidopsis thaliana) named AtRAD51C and AtXRCC3, which are homologs of human RAD51C and XRCC3, respectively, and described the interaction of their products in a yeast two-hybrid system. Recent studies showed the involvement of AtXrcc3 in DNA repair and functional role in meiosis. To determine the role of RAD51C in meiotic and mitotic recombination in higher plants, we characterized a T-DNA insertion mutant of AtRAD51C. Although the atrad51C mutant grew normally during vegetative developmental stage, the mutant produced aborted siliques, and their anthers did not contain mature pollen grains. Crossing of the mutant with wild-type plants showed defective male and female gametogeneses as evidenced by lack of seed production. Furthermore, meiosis was severely disturbed in the mutant. The atrad51C mutant also showed increased sensitivity to g-irradiation and cisplatin, which are known to induce double-strand DNA breaks. The efficiency of homologous recombination in somatic cells in the mutant was markedly reduced relative to that in wild-type plants.

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Section: Discussionmentioning

confidence: 99%

Arabidopsis RAD51C Gene Is Important for Homologous Recombination in Meiosis and Mitosis

et al. 2005

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“…8 Repair of DNA double-strand breaks during the G1/S and S/ G2 phases of the mitotic cell cycle occurs through 2 main mechanisms, non-homologous end-joining and homologous recombination. [11][12][13] Of these, the homologous recombination is an error-free repair mechanism and its proper function is critical for maintaining the chromosomal integrity. 12 BRCA2 functions in homologous recombination together with RAD51 recombinase and colocalizes to the sites of DNA damage.…”

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confidence: 99%

Mutations in the BRCA2 interacting DSS1 are not a risk factor for male breast cancer

Syrjäkoski

Jäntti

Kallioniemi

et al. 2006

Intl Journal of Cancer

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Male breast cancer (MBC) is a rare disease and, because of its rarity, its etiology is poorly understood. However, germ-line mutations in breast cancer susceptibility gene BRCA2 are known to predispose to MBC. 1 Male carriers of BRCA2 mutations have an 80-100 times high risk for the development of breast cancer than the general male population thus making BRCA2 the strongest presently known MBC linked gene. 2 In addition to BRCA2, germ-line mutations in BRCA1, CHEK2, AR and PTEN have also been linked to increased MBC risk, 1 thus further supporting the role of genetic predisposition in the development of MBC. However, only a proportion of MBC cases ( 4-40% depending on the population) can be explained by mutations in BRCA2 and these other susceptibility genes. 1,3 Defects in genes functionally linked to BRCA2 might account for additional MBC cases. One such candidate gene is DSS1 (also known as SHFM1 and SEM1). DSS1 (deleted in split hand/split foot) encodes a 70 amino acids long, structurally and functionally highly conserved protein. [4][5][6] The gene was originally linked with split hand/split foot malformation (SHFM) on chromosome 7q21.3-q22.1 4 , but no definitive evidence for its role in this syndrome has been found. 7 Instead, DSS1 has been shown to interact directly with BRCA2. 6 Interactions of BRCA2 and DSS1, or their orthologues in lower organisms, have been convincingly demonstrated at least in yeast, fungi and mammalian cells. 6,8,9 The physical binding between these 2 proteins occurs in the most conserved portions of both proteins. 6,8 Interestingly, some of the known cancer predisposing mutations in BRCA2 affect amino acids that mediate the interaction of DSS1 with BRCA2 and, essentially all BRCA2 in mammalian cells is associated with DSS1. 8,10 Most importantly, the strong physical interaction between DSS1 and BRCA2 seems to be crucial for the BRCA2 function in the repair of DNA double-strand breaks. 8 Repair of DNA double-strand breaks during the G1/S and S/ G2 phases of the mitotic cell cycle occurs through 2 main mechanisms, non-homologous end-joining and homologous recombination. [11][12][13] Of these, the homologous recombination is an error-free repair mechanism and its proper function is critical for maintaining the chromosomal integrity. 12 BRCA2 functions in homologous recombination together with RAD51 recombinase and colocalizes to the sites of DNA damage. 14,15 Interestingly, Yang et al. 8 demonstrated that the same 90-kDa BRCA2 domain that binds to DSS1 also binds to singlestranded DNA. The function of DSS1 in this interaction remained unclear but DSS1 may regulate the accessibility of the DNA binding sites on BRCA2. 8 This model raises both DSS1 and BRCA2 in critical role in homologous recombination. In fact, loss of DSS1 function has been shown to result in highly similar phenotypes in DNA repair and homologous recombination than inactivation of BRCA2 or RAD51. 9,[16][17][18] Furthermore, DSS1 is needed for DNA damage-induced RAD51 locus formation and is recruited to double strand...

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“…The BCDX2 complex binds to nicks of duplex DNA and exhibits ATPase activity in vitro. 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].…”

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

confidence: 70%

“…Mutant analysis of RAD51B in a chicken B lymphocyte DT40 cell line indicates that RAD51B is important for maintaining genome integrity and for homologous recombinational repair [107,108]. However, the rad51b mutant cell line is viable; although about 20% cells die after each division as a result of spontaneous chromosomal aberrations, indicating that RAD51B is required for repairing DNA breaks or damages under normal growth conditions.…”

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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The Rad51 Paralog Rad51B Promotes Homologous Recombinational Repair

Cited by 243 publications

References 67 publications

Arabidopsis RAD51C Gene Is Important for Homologous Recombination in Meiosis and Mitosis

Arabidopsis RAD51C Gene Is Important for Homologous Recombination in Meiosis and Mitosis

Mutations in the BRCA2 interacting DSS1 are not a risk factor for male breast cancer

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

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