Abstract
We demonstrate that the absence of E2F1 leads to spontaneous DNA breaks and impaired recovery following exposure to ionizing radiation. E2F1 deficiency results in defective NBS1 phosphorylation and foci formation in response to DSBs but does not affect NBS1 expression levels. Moreover, an increased...
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PMID: 21512314
PDF is available here.
Abstract
We show that single-strand lesions produced by the alkylating agent methyl methanesulfonate (MMS) can generate DSBs in G2-arrested cells, i.e., S-phase independent. These derived DSBs were observed in apn1/2 endonuclease mutants and resulted from aborted base excision repair leading to 3' blocked si...
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PMID: 21552545
PDF is available here.
Abstract
We used fluorescence microscopy and 3-dimensional image analysis to compare mESC and differentiated cells, with regard to HR-mediated repair of spontaneous and X-ray-induced double-strand breaks (DSBs). Microscopic analysis of repair foci, flow cytometry, and functional assays of the major DSB repai...
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PMID: 20491544
PDF is available here.
Abstract
We identify a mechanism in which EZH2 expression-mediated downregulation of DNA damage repair leads to accumulation of recurrent RAF1 gene amplification in BTICs, which activates p-ERK-β-catenin signaling to promote BTIC expansion. We further reveal that AZD6244, a clinical trial drug that inhibits...
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PMID: 21215703
PDF is available here.
Sophie Badie,
Jose M Escandell,
Peter Bouwman,
Ana Rita Carlos,
Maria Thanasoula,
Maria M Gallardo,
Anitha Suram,
Isabel Jaco,
Javier Benitez,
Utz Herbig,
Maria A Blasco,
Jos Jonkers and
Madalena Tarsounas
Abstract
We show that BRCA2 associates with telomeres during the S and G2 phases of the cell cycle and facilitates the loading of RAD51 onto telomeres. Conditional deletion of Brca2 and inhibition of Rad51 in mouse embryonic fibroblasts (MEFs), but not inactivation of Brca1, led to shortening of telomeres an...
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PMID: 21076401
PDF is available here.
Abstract
We found that depletion of mammalian homologs of Bre1 compromises the response to ionizing radiation, leading to increased radiosensitivity and a G(2)/M checkpoint defect. The deficiency in Bre1a/b function was also associated with increased sensitivity to crosslinking drugs and defective formation...
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PMID: 20738173
PDF is available here.
Abstract
Overexpression of RAD51, a key component of the homologous DNA repair pathway, is associated with poor breast cancer outcome. This finding warrants prospective studies of RAD51 as a prognosticator and therapeutic target.
2010 Elsevier Inc. All rights reserved....
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PMID: 20092964
PDF is available here.
Abstract
We describe an alternative mode of linear chromosome maintenance in which canonical telomeres are superseded by blocks of heterochromatin. We show that in the absence of telomerase, Schizosaccharomyces pombe cells can survive telomere sequence loss by continually amplifying and rearranging heterochr...
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PMID: 20829796
PDF is available here.
Abstract
We have previously shown that a 28-amino acid peptide derived from the BRC4 motif of BRCA2 tumor suppressor inhibits selectively human RAD51 recombinase (HsRad51). With the aim of designing better inhibitors for cancer treatment, we combined an in silico docking approach with in vitro biochemical te...
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PMID: 20684611
PDF is available here.
Abstract
We analyzed replication and recombination intermediates in a well-defined fission yeast system that blocks replication forks. We show that, in response to fork arrest, chromosomal rearrangements result from Rad52-dependent nascent strand template exchange occurring during fork restart. This template...
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PMID: 20705238
PDF is available here.
Abstract
This is the first study evaluating the effect of the RAD51 G135C polymorphism in NSCLC patient survival. Our results suggest that RAD51 genotypes could be useful molecular markers for predicting the clinical outcome of NSCLC patients....
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PMID: 19960343
PDF is available here.
Abstract
We demonstrated previously that expression of simian virus 40 (SV40) large T antigen (LT), without a viral origin, is sufficient to induce the hallmarks of a cellular DNA damage response (DDR), such as focal accumulation of gamma-H2AX and 53BP1, via Bub1 binding. Here we expand our characterization...
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PMID: 20519379
PDF is available here.
Meredith A Morgan,
Leslie A Parsels,
Lili Zhao,
Joshua D Parsels,
Mary A Davis,
Maria C Hassan,
Sankari Arumugarajah,
Linda Hylander-Gans,
Deborah Morosini,
Diane M Simeone,
Christine E Canman,
Daniel P Normolle,
Sonya D Zabludoff,
Jonathan Maybaum and
Theodore S Lawrence
Abstract
We have combined a Chk1/2-targeted agent, AZD7762, currently in phase I clinical trials, with gemcitabine and ionizing radiation in preclinical pancreatic tumor models. We found that in vitro AZD7762 alone or in combination with gemcitabine significantly sensitized MiaPaCa-2 cells to radiation. AZD7...
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PMID: 20501833
PDF is available here.
Abstract
We show that XRCC2 is highly conserved and that most substantial truncations of the protein destroy its ability to function. XRCC2 and its partner protein RAD51L3 are found to interact with RAD51 in the 2-hybrid system, and XRCC2 is shown to be important but not essential for the accumulation of RAD...
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PMID: 20189471
PDF is available here.
Abstract
We have examined the role of RAD51 in the only plant that exhibits high GT frequencies, the model bryophyte Physcomitrella patens. Our results show that the two RAD51 proteins have partially redundant functions in the maintenance of genome integrity and resistance to ionizing radiation. Furthermore,...
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PMID: 20189889
PDF is available here.
Abstract
The SOS screen, as originally described by Perkins et al. (1999) [7], was setup with the aim of identifying Arabidopsis functions that might potentially be involved in the DNA metabolism. Such functions, when expressed in bacteria, are prone to disturb replication and thus trigger the SOS response....
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PMID: 20227352
PDF is available here.
Abstract
We have cloned and characterized the RAD51 and RAD59 orthologs of the pathogenic fungus Candida albicans. CaRad51 exhibited more than 50% identity with several other eukaryotes and the conserved the catalytic domain of a bacterial RecA. As compared to the parental strain, null strains of rad51 exhib...
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PMID: 20206282
PDF is available here.
Abstract
Several markers of malignancy have been proposed for canine mammary tumors on the mRNA and protein levels. However, their association with tumor malignancy applies only for mean values of large groups of tumors, but no single marker identified to date can be used to reliably predict malignancy for i...
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PMID: 20375427
PDF is available here.
Abstract
We have used time-lapse microscopy, recently developed cytokinesis assays and BAC recombineering (bacterial artificial chromosome recombinogenic engineering) to investigate the function and localization of BRCA2 during cell division. Our analysis suggests that BRCA2 does not regulate cytokinesis in...
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PMID: 20356927
PDF is available here.
Abstract
We purified human SPF45 and found that it preferentially binds to the Holliday junction, which is a key DNA intermediate in the homologous-recombination pathway. Deletion analyses revealed that the RNA recognition motif, which is located in the C-terminal region of human SPF45, is not involved in DN...
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PMID: 20236180
PDF is available here.
Abstract
We show that human protein phosphatase 4 (PP4) dephosphorylates replication protein A (RPA) subunit RPA2, regulating its role in the DSB response. PP4R2, a regulatory subunit of PP4, mediates the DNA damage-dependent association between RPA2 and the PP4C catalytic subunit. PP4 efficiently dephosphor...
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PMID: 20154705
PDF is available here.
Abstract
We show that the RPA4 gene is expressed in normal human tissues and that its expression is decreased in cancerous tissues. To determine whether aRPA plays a role in cellular physiology, we investigated its role in DNA repair. aRPA interacted with both Rad52 and Rad51 and stimulated Rad51 strand exch...
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PMID: 19996105
PDF is available here.
Abstract
We have previously described an assay in S. cerevisiae that allows us to model how repair of multiple breaks leads to the formation of chromosomal translocations by single-strand annealing (SSA) and found that Rad59, a paralog of the single-stranded DNA annealing protein Rad52, is critically importa...
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PMID: 20012294
PDF is available here.
Abstract
We have previously described an assay in S. cerevisiae that allows us to model how repair of multiple breaks leads to the formation of chromosomal translocations by single-strand annealing (SSA) and found that Rad59, a paralog of the single-stranded DNA annealing protein Rad52, is critically importa...
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PMID: 20012294
PDF is available here.
Abstract
We have previously described an assay in S. cerevisiae that allows us to model how repair of multiple breaks leads to the formation of chromosomal translocations by single-strand annealing (SSA) and found that Rad59, a paralog of the single-stranded DNA annealing protein Rad52, is critically importa...
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PMID: 20012294
PDF is available here.
Abstract
We have previously described an assay in S. cerevisiae that allows us to model how repair of multiple breaks leads to the formation of chromosomal translocations by single-strand annealing (SSA) and found that Rad59, a paralog of the single-stranded DNA annealing protein Rad52, is critically importa...
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PMID: 20012294
PDF is available here.
Abstract
We have previously described an assay in S. cerevisiae that allows us to model how repair of multiple breaks leads to the formation of chromosomal translocations by single-strand annealing (SSA) and found that Rad59, a paralog of the single-stranded DNA annealing protein Rad52, is critically importa...
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PMID: 20012294
PDF is available here.
Abstract
We have previously described an assay in S. cerevisiae that allows us to model how repair of multiple breaks leads to the formation of chromosomal translocations by single-strand annealing (SSA) and found that Rad59, a paralog of the single-stranded DNA annealing protein Rad52, is critically importa...
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PMID: 20012294
PDF is available here.
Abstract
We have previously described an assay in S. cerevisiae that allows us to model how repair of multiple breaks leads to the formation of chromosomal translocations by single-strand annealing (SSA) and found that Rad59, a paralog of the single-stranded DNA annealing protein Rad52, is critically importa...
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PMID: 20012294
PDF is available here.
Abstract
We show that PARP inhibition to block BER is toxic to hypoxic cancer cells, in which homology-dependent repair (HDR) is known to be down-regulated. However, we also report the unexpected finding that disruption of PARP, itself, either via chemical PARP inhibitors or siRNAs targeted to PARP-1, can in...
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PMID: 20133863
PDF is available here.
Abstract
We identified here the recently discovered polymerase POLN to be involved in repair of DNA cross-links. Such DNA lesions are highly toxic and are believed to be repaired by the sequential activity of nucleotide excision repair, translesion synthesis, and homologous recombination mechanisms. By funct...
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PMID: 19995904
PDF is available here.
Karina B Falbo,
Constance Alabert,
Yuki Katou,
Su Wu,
Junhong Han,
Tammy Wehr,
Jing Xiao,
Xiangwei He,
Zhiguo Zhang,
Yang Shi,
Katsu Shirahige,
Philippe Pasero and
Xuetong Shen
Abstract
We reveal a specific function of the yeast INO80 chromatin remodeling complex in the DNA damage tolerance pathways. Whereas INO80 is necessary for the resumption of replication at forks stalled by methyl methane sulfonate (MMS), it is not required for replication fork collapse after treatment with h...
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PMID: 19855395
PDF is available here.
Abstract
We have examined the mechanism of disassembly of Rad51 nucleoprotein filaments by Srs2 and find that a physical interaction between Rad51 and the C-terminal region of Srs2 triggers ATP hydrolysis within the Rad51 filament, causing Rad51 to dissociate from DNA. This allosteric mechanism explains the...
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PMID: 19595720
PDF is available here.
Abstract
We examined mRNA and protein expression of hMLH3 compared to other human MSH and MLH in a panel of human tissues and the HeLa cell line. Quantitative PCR suggests that MSH and MLH transcripts are expressed ubiquitously. hMLH3 mRNA is present at low levels in numerous tissues. Protein expression appe...
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PMID: 19483466
PDF is available here.
Abstract
We show that MCPH1 binds to BRCA2 and regulates the localization of BRCA2 and Rad51 at sites of DNA damage. The interaction occurs through the NH(2) terminus of BRCA2 and the COOH terminal BRCT domains of MCPH1. Disruption of the interaction between MCPH1 and BRCA2 has no effect on the ability of BR...
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PMID: 19549900
PDF is available here.
Abstract
We reveal novel properties of the BRCA2-associated protein PALB2 in the assembly of the recombinational DNA repair machinery at DNA damage sites. Although the chromatin association of PALB2 is a prerequisite for subsequent BRCA2 and RAD51 loading, the focal accumulation of the PALB2 x BRCA2 x RAD51...
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PMID: 19423707
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
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PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
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PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
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PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
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PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
|
PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
|
PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
|
PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
|
PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
|
PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
|
PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
|
PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
|
PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
|
PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
|
PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
|
PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
|
PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
|
PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
|
PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
|
PMID: 19427856
PDF is available here.
Abstract
We prepared two specific antibodies that selectively detected the Tyr54 or Tyr315 phosphorylation site of Rad51. By co-transfection of HeLa cells with c-Abl and Rad51, we clearly showed that both Tyr54 and Tyr315 of Rad51 are phosphorylated by c-Abl. Furthermore, we showed that the phosphorylation o...
|
PMID: 19427856
PDF is available here.