Genomes and Genes
Experts and Doctors on dna repair in Toronto, Ontario, Canada
Locale: Toronto, Ontario, Canada
Topic: dna repair
- Wells P, McCallum G, Lam K, Henderson J, Ondovcik S. Oxidative DNA damage and repair in teratogenesis and neurodevelopmental deficits. Birth Defects Res C Embryo Today. 2010;90:103-9 pubmed publisher..Protection may be variably dependent upon such factors as the nature of the teratogen and its concentration within the embryo, the stage of development, the species, strain, gender, target tissue and cell type, among other factors. ..
- Fan R, Kumaravel T, Jalali F, Marrano P, Squire J, Bristow R. Defective DNA strand break repair after DNA damage in prostate cancer cells: implications for genetic instability and prostate cancer progression. Cancer Res. 2004;64:8526-33 pubmed..Our findings support the development of novel treatment strategies designed to reinstate normal DNA repair in prostate cancer cells. ..
- Panigrahi G, Slean M, Simard J, Pearson C. Human mismatch repair protein hMutL? is required to repair short slipped-DNAs of trinucleotide repeats. J Biol Chem. 2012;287:41844-50 pubmed publisher..The joint involvement of hMutS? and hMutL? suggests that repeat instability may be the result of aberrant outcomes of repair attempts. ..
- Wang A, Agrawal A. DNA repair pathway choice is influenced by the health of Drosophila melanogaster. Genetics. 2012;192:361-70 pubmed publisher..Finally, we observe that the effect of larval diet on adult repair increases as flies age, indicating that developmental differences early in life can have long-lasting consequences. ..
- Kato H, Ito E, Shi W, Alajez N, Yue S, Lee C, et al. Efficacy of combining GMX1777 with radiation therapy for human head and neck carcinoma. Clin Cancer Res. 2010;16:898-911 pubmed publisher..Therefore, GMX1777 combined with radiotherapy definitely warrants clinical evaluation in human head and neck cancer patients. ..
- Halaby M, Hakem A, Li L, El Ghamrasni S, Venkatesan S, Hande P, et al. Synergistic interaction of Rnf8 and p53 in the protection against genomic instability and tumorigenesis. PLoS Genet. 2013;9:e1003259 pubmed publisher..Altogether, the data in this study highlight the importance of p53-pathway activation upon loss of Rnf8, suggesting that Rnf8 and p53 functionally interact to protect against genomic instability and tumorigenesis...
- Lal G, Ash C, Hay K, Redston M, Kwong E, Hancock B, et al. Suppression of intestinal polyps in Msh2-deficient and non-Msh2-deficient multiple intestinal neoplasia mice by a specific cyclooxygenase-2 inhibitor and by a dual cyclooxygenase-1/2 inhibitor. Cancer Res. 2001;61:6131-6 pubmed..Therefore, specific COX-2 inhibitors may be useful as chemopreventive and therapeutic agents in humans at risk for colorectal neoplasia...
- Bassi C, Ho J, Srikumar T, Dowling R, Gorrini C, Miller S, et al. Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress. Science. 2013;341:395-9 pubmed publisher..Our findings may have implications for individualized therapy for patients with PTEN-deficient tumors. ..
- Strathdee C, Duncan A, Buchwald M. Evidence for at least four Fanconi anaemia genes including FACC on chromosome 9. Nat Genet. 1992;1:196-8 pubmed..3 through in situ hybridization. These results suggest that mutations in at least four different genes lead to FA, a degree of genetic heterogeneity comparable to that of other DNA repair disorders. ..
- Kotsopoulos J, Chen Z, Vallis K, Poll A, Ghadirian P, Kennedy G, et al. Toenail selenium status and DNA repair capacity among female BRCA1 mutation carriers. Cancer Causes Control. 2010;21:679-87 pubmed publisher..These results provide evidence for a possible protective effect of selenium against BRCA1-associated breast cancers. ..
- Macrae C, McCulloch R, Ylanko J, Durocher D, Koch C. APLF (C2orf13) facilitates nonhomologous end-joining and undergoes ATM-dependent hyperphosphorylation following ionizing radiation. DNA Repair (Amst). 2008;7:292-302 pubmed..Collectively, these results suggest that APLF is an ATM target that is involved in NHEJ and facilitates DSB repair, likely via interactions with Ku and XRCC4-DNA ligase IV. ..
- Eskiw C, Dellaire G, Mymryk J, Bazett Jones D. Size, position and dynamic behavior of PML nuclear bodies following cell stress as a paradigm for supramolecular trafficking and assembly. J Cell Sci. 2003;116:4455-66 pubmed..PML bodies may provide a useful paradigm for the dynamics and integrity of other supramolecular protein complexes involved in processes such as transcription, RNA processing DNA repair and replication...
- Dellaire G, Ching R, Ahmed K, Jalali F, Tse K, Bristow R, et al. Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and ATR. J Cell Biol. 2006;175:55-66 pubmed..Therefore, an increase in PML NB number is an intrinsic element of the cellular response to DNA damage...
- Luoto K, Meng A, Wasylishen A, Zhao H, Coackley C, Penn L, et al. Tumor cell kill by c-MYC depletion: role of MYC-regulated genes that control DNA double-strand break repair. Cancer Res. 2010;70:8748-59 pubmed publisher..Our results suggest that anti-MYC agents may target cells to prevent genetic instability but would not lead to differential radiosensitization or chemosensitization...
- Savas S, Ozcelik H. Phosphorylation states of cell cycle and DNA repair proteins can be altered by the nsSNPs. BMC Cancer. 2005;5:107 pubmed
- Lee C, Goncalves L, Wells P. Resistance of CD-1 and ogg1 DNA repair-deficient mice to thalidomide and hydrolysis product embryopathies in embryo culture. Toxicol Sci. 2011;122:146-56 pubmed publisher..However, DNA repair-deficient ogg1 knockout mice proved resistant to TD-initiated embryopathies in culture and teratogenesis in vivo, indicating that the resistance of mice is not due to a higher level of DNA repair. ..
- Bohgaki T, Bohgaki M, Cardoso R, Panier S, Zeegers D, Li L, et al. Genomic instability, defective spermatogenesis, immunodeficiency, and cancer in a mouse model of the RIDDLE syndrome. PLoS Genet. 2011;7:e1001381 pubmed publisher..These results highlight a central role for RNF168 in the hierarchical network of DNA break signaling that maintains genomic integrity and suppresses cancer development in mammals. ..
- Bradshaw P, Stavropoulos D, Meyn M. Human telomeric protein TRF2 associates with genomic double-strand breaks as an early response to DNA damage. Nat Genet. 2005;37:193-7 pubmed..Our results implicate TRF2 in an initial stage of DSB recognition and processing that occurs before association of ATM with DSBs and activation of the ATM-dependent DSB response network. ..
- Iampietro C, Bergalet J, Wang X, Cody N, Chin A, Lefebvre F, et al. Developmentally regulated elimination of damaged nuclei involves a Chk2-dependent mechanism of mRNA nuclear retention. Dev Cell. 2014;29:468-81 pubmed publisher..These results reveal a layer of regulation within the DNA damage surveillance systems that safeguard genome integrity in eukaryotes. ..
- Ramaekers C, Wouters B. Regulatory functions of ubiquitin in diverse DNA damage responses. Curr Mol Med. 2011;11:152-69 pubmed
- Bradbury P, Kulke M, Heist R, Zhou W, Ma C, Xu W, et al. Cisplatin pharmacogenetics, DNA repair polymorphisms, and esophageal cancer outcomes. Pharmacogenet Genomics. 2009;19:613-25 pubmed publisher..1-5.5) to 3.73 (95% CI: 1.6-8.7). Haplotype analyses affirmed these results. DNA repair polymorphisms are associated with OS and PFS, and if validated may predict for benefit from cisplatin therapy in patients with esophageal cancer. ..
- Kan Y, Batada N, Hendrickson E. Human somatic cells deficient for RAD52 are impaired for viral integration and compromised for most aspects of homology-directed repair. DNA Repair (Amst). 2017;55:64-75 pubmed publisher..In toto, our work demonstrates that RAD52 contributes to the maintenance of genome stability and tumor suppression in human cells. ..
- Fillingham J, Greenblatt J. A histone code for chromatin assembly. Cell. 2008;134:206-8 pubmed publisher..Chen et al. (2008) establish that the acetylation mark promotes chromatin reassembly following DNA double-strand break repair. ..
- Laposa R, Henderson J, Xu E, Wells P. Atm-null mice exhibit enhanced radiation-induced birth defects and a hybrid form of embryonic programmed cell death indicating a teratological suppressor function for ATM. FASEB J. 2004;18:896-8 pubmed..These results show that Atm is a novel teratologic suppressor gene protecting embryos from pathological cell death and teratogenesis initiated by even mild DNA damage. ..
- Braun D, Rao J, Mollet G, Schapiro D, Daugeron M, Tan W, et al. Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly. Nat Genet. 2017;49:1529-1538 pubmed publisher..We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms. ..
- Al Rashid S, Dellaire G, Cuddihy A, Jalali F, Vaid M, Coackley C, et al. Evidence for the direct binding of phosphorylated p53 to sites of DNA breaks in vivo. Cancer Res. 2005;65:10810-21 pubmed
- Dellaire G, Bazett Jones D. PML nuclear bodies: dynamic sensors of DNA damage and cellular stress. Bioessays. 2004;26:963-77 pubmed..The dramatically increased total surface area available would enhance interactions between PML-associated factors regulating DNA repair and apoptosis...
- Osborne L, Herbrick J, Greavette T, Heng H, Tsui L, Scherer S. PMS2-related genes flank the rearrangement breakpoints associated with Williams syndrome and other diseases on human chromosome 7. Genomics. 1997;45:402-6 pubmed..22, 7q11.23, and 7q22. Within 7q11.23, human PMS2L genes were found to be present at at least three sites as part of duplicated genomic segments that flank the most common rearrangement breakpoints in Williams syndrome. ..
- Ross A, Li M, Yu B, Gao M, Derry W. The EEL-1 ubiquitin ligase promotes DNA damage-induced germ cell apoptosis in C. elegans. Cell Death Differ. 2011;18:1140-9 pubmed publisher..Although ee1-1 mutants exhibit hypersensitivity to genotoxic stress they do not appear to be defective in DNA repair, suggesting a distinct role for EEL-1 in promoting damage-induced apoptosis in the germline. ..
- Martin A, Li Z, Lin D, Bardwell P, Iglesias Ussel M, Edelmann W, et al. Msh2 ATPase activity is essential for somatic hypermutation at a-T basepairs and for efficient class switch recombination. J Exp Med. 2003;198:1171-8 pubmed..These results indicate that Msh2 adenosine triphosphatase activity is required for A-T mutations, and suggest that Msh2 has more than one role in CSR. ..
- Tang E, Martin A. Immunoglobulin gene conversion: synthesizing antibody diversification and DNA repair. DNA Repair (Amst). 2007;6:1557-71 pubmed..These insights, combined with those from the common mechanism of AID action, synergize to develop an emerging picture of the mechanism underlying IGC. ..
- Kumar A, Beloglazova N, Bundalovic Torma C, Phanse S, Deineko V, Gagarinova A, et al. Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coli. Cell Rep. 2016;14:648-661 pubmed publisher..Analyses of pan-bacterial conservation patterns suggest that DDR mechanisms and functional relationships are near universal, highlighting a modular and highly adaptive genomic stress response. ..
- Zhang W, Durocher D. De novo telomere formation is suppressed by the Mec1-dependent inhibition of Cdc13 accumulation at DNA breaks. Genes Dev. 2010;24:502-15 pubmed publisher..These studies therefore identify a mechanism by which the ATR family of kinases enforces genome integrity, and a process that underscores the contribution of Cdc13 to the fate of DNA ends. ..
- Koch C, Agyei R, Galicia S, Metalnikov P, O DONNELL P, Starostine A, et al. Xrcc4 physically links DNA end processing by polynucleotide kinase to DNA ligation by DNA ligase IV. EMBO J. 2004;23:3874-85 pubmed..Therefore, these results suggest a new role for Xrcc4 in the coordination of DNA end processing with DNA ligation. ..
- Perez Ordonez B, Huynh N, Berean K, Jordan R. Expression of mismatch repair proteins, beta catenin, and E cadherin in intestinal-type sinonasal adenocarcinoma. J Clin Pathol. 2004;57:1080-3 pubmed..Despite their histological resemblance to colorectal adenocarcinomas, there is little information about the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinomas (ITACs)...
- Tamblyn L, Li E, Sarras H, Srikanth P, Hande M, McPherson J. A role for Mus81 in the repair of chromium-induced DNA damage. Mutat Res. 2009;660:57-65 pubmed publisher..Our findings support a role for Mus81 in the resolution of replication-associated DNA damage associated with this genotoxic agent, by converting Cr[VI]-DNA lesions into a form more amenable for homologous recombination. ..
- Ramaekers C, van den Beucken T, Meng A, Kassam S, Thoms J, Bristow R, et al. Hypoxia disrupts the Fanconi anemia pathway and sensitizes cells to chemotherapy through regulation of UBE2T. Radiother Oncol. 2011;101:190-7 pubmed publisher..This pathway can potentially be exploited to target hypoxic cells in tumors. ..
- Salsman J, Jagannathan M, Paladino P, Chan P, Dellaire G, Raught B, et al. Proteomic profiling of the human cytomegalovirus UL35 gene products reveals a role for UL35 in the DNA repair response. J Virol. 2012;86:806-20 pubmed publisher..Therefore, the identified interactions suggest that UL35 can contribute to viral replication through the manipulation of host responses...
- He Z, Wong J, Maniar H, Brill S, Ingles C. Assessing the requirements for nucleotide excision repair proteins of Saccharomyces cerevisiae in an in vitro system. J Biol Chem. 1996;271:28243-9 pubmed..These data indicate that Rpa is an essential component of the NER machinery in S. cerevisiae as it is in mammalian cells. ..
- Bielas J, Heddle J. Elevated mutagenesis and decreased DNA repair at a transgene are associated with proliferation but not apoptosis in p53-deficient cells. Proc Natl Acad Sci U S A. 2003;100:12853-8 pubmed..The role of apoptosis in vivo, however, may be to remove whole tissue subpopulations that can be renewed by less sensitive stem cells. ..
- Leung K, Abou El Hassan M, Bremner R. A rapid and efficient method to purify proteins at replication forks under native conditions. Biotechniques. 2013;55:204-6 pubmed publisher..This faster, higher-yield method will facilitate MS analysis of replication fork complexes. ..
- Vassileva V, Millar A, Briollais L, Chapman W, Bapat B. Genes involved in DNA repair are mutational targets in endometrial cancers with microsatellite instability. Cancer Res. 2002;62:4095-9 pubmed
- Nagy A, Moens C, Ivanyi E, Pawling J, Gertsenstein M, Hadjantonakis A, et al. Dissecting the role of N-myc in development using a single targeting vector to generate a series of alleles. Curr Biol. 1998;8:661-4 pubmed..This, and the possibility of subsequent lineage-specific or conditional allele repair in situ, represent new genome modification strategies that can be used to investigate multiple functions of a single gene. ..
- Nakada S, Chen G, Gingras A, Durocher D. PP4 is a gamma H2AX phosphatase required for recovery from the DNA damage checkpoint. EMBO Rep. 2008;9:1019-26 pubmed publisher..Taken together, these results indicate that PP4 is an evolutionarily conserved gammaH2AX phosphatase. ..
- Wilhelm M, Rufini A, Wetzel M, Tsuchihara K, Inoue S, Tomasini R, et al. Isoform-specific p73 knockout mice reveal a novel role for delta Np73 in the DNA damage response pathway. Genes Dev. 2010;24:549-60 pubmed publisher..This novel finding may explain why human tumors with high levels of DeltaNp73 expression show enhanced resistance to chemotherapy. ..
- Gadsden M, McIntosh E, Game J, Wilson P, Haynes R. dUTP pyrophosphatase is an essential enzyme in Saccharomyces cerevisiae. EMBO J. 1993;12:4425-31 pubmed..These results are in general agreement with previous models in thymine-less death that implicate dUTP metabolism. They also suggest an alternative approach for chemotherapeutic drug design. ..
- Tang E, Martin A. NHEJ-deficient DT40 cells have increased levels of immunoglobulin gene conversion: evidence for a double strand break intermediate. Nucleic Acids Res. 2006;34:6345-51 pubmed..These data suggest that a DSB is the major DNA lesion that initiates GC. ..
- Harding S, Bristow R. Discordance between phosphorylation and recruitment of 53BP1 in response to DNA double-strand breaks. Cell Cycle. 2012;11:1432-44 pubmed publisher..As relative 53BP1 expression may be a biomarker of DNA repair capacity in solid tumors, the tracking of 53BP1 phosphoforms in situ may give unique information regarding different cancer phenotypes or response to cancer treatment. ..
- Ali M, Kim H, Cleary S, Cupples C, Gallinger S, Bristow R. Characterization of mutant MUTYH proteins associated with familial colorectal cancer. Gastroenterology. 2008;135:499-507 pubmed publisher..This study of MUTYH mutants suggests that certain SNPs may be as partially dysfunctional in base excision repair as missense-MUTYH mutants and lead to colorectal carcinogenesis. ..
- Abraham J, Lemmers B, Hande M, Moynahan M, Chahwan C, Ciccia A, et al. Eme1 is involved in DNA damage processing and maintenance of genomic stability in mammalian cells. EMBO J. 2003;22:6137-47 pubmed..Most importantly, Eme1 deficiency led to spontaneous genomic instability. These results reveal that mammalian Eme1 plays a key role in DNA repair and the maintenance of genome integrity. ..
- Szilard R, Durocher D. Telomere protection: an act of God. Curr Biol. 2006;16:R544-6 pubmed..New work has revealed that Apollo, a nuclease previously implicated in DNA repair, also has a role in safeguarding telomeres during S phase. ..
- Agnihotri S, Gajadhar A, Ternamian C, Gorlia T, Diefes K, Mischel P, et al. Alkylpurine-DNA-N-glycosylase confers resistance to temozolomide in xenograft models of glioblastoma multiforme and is associated with poor survival in patients. J Clin Invest. 2012;122:253-66 pubmed publisher..Collectively, our data demonstrate that APNG contributes to TMZ resistance in GBM and may be useful in the diagnosis and treatment of the disease. ..
- Figueiredo J, Knight J, Briollais L, Andrulis I, Ozcelik H. Polymorphisms XRCC1-R399Q and XRCC3-T241M and the risk of breast cancer at the Ontario site of the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev. 2004;13:583-91 pubmed..Our results suggest that these polymorphisms may influence breast cancer risk by modifying the effect of risk factors such as FH. There is a need for further study into the role of these polymorphisms as effect modifiers. ..
- Slean M, Reddy K, Wu B, Nichol Edamura K, Kekis M, Nelissen F, et al. Interconverting conformations of slipped-DNA junctions formed by trinucleotide repeats affect repair outcome. Biochemistry. 2013;52:773-85 pubmed publisher..Thus, slipped-junction structure can determine whether repair attempts lead to correction or expansion mutations. ..
- Tse D, Zhai R, Zhou W, Heist R, Asomaning K, Su L, et al. Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk. Cancer Causes Control. 2008;19:1077-83 pubmed publisher..There is evidence of an additive role for SNPs along a common DNA repair pathway. Future larger studies of esophageal adenocarcinoma etiology should evaluate entire biological pathways. ..
- Slean M, Panigrahi G, RANUM L, Pearson C. Mutagenic roles of DNA "repair" proteins in antibody diversity and disease-associated trinucleotide repeat instability. DNA Repair (Amst). 2008;7:1135-54 pubmed publisher..Here we review and compare the mutagenic role of DNA "repair" proteins in the processes of SHM, CSR and TNR instability. ..
- Mark W, Liao J, Lu Y, Ayed A, Laister R, Szymczyna B, et al. Characterization of segments from the central region of BRCA1: an intrinsically disordered scaffold for multiple protein-protein and protein-DNA interactions?. J Mol Biol. 2005;345:275-87 pubmed..This supports a model in which the central region may act as a long flexible scaffold for intermolecular interactions, thereby helping to integrate multiple signals in the DNA damage response pathway. ..
- Fraser M, Harding S, Zhao H, Coackley C, Durocher D, Bristow R. MRE11 promotes AKT phosphorylation in direct response to DNA double-strand breaks. Cell Cycle. 2011;10:2218-32 pubmed..Thus, these data directly link the presence of DNA breaks to AKT-mediated cell survival and support AKT as a target for cancer therapy. ..
- Escribano D az C, Orthwein A, Fradet Turcotte A, Xing M, Young J, Tk J, et al. A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice. Mol Cell. 2013;49:872-83 pubmed publisher..This work therefore identifies a cell cycle-regulated circuit, underpinned by RIF1 and BRCA1, that governs DSB repair pathway choice to ensure that NHEJ dominates in G1 and HR is favored from S phase onward...
- Memarian N, Jessulat M, Alirezaie J, Mir Rashed N, Xu J, Zareie M, et al. Colony size measurement of the yeast gene deletion strains for functional genomics. BMC Bioinformatics. 2007;8:117 pubmed..GD offers significant improvement over the manual inspection method to detect relative yeast colony size differences. The speed and accuracy associated with GD makes it an ideal choice for large-scale functional genomics investigations. ..
- Bohgaki M, Bohgaki T, El Ghamrasni S, Srikumar T, Maire G, Panier S, et al. RNF168 ubiquitylates 53BP1 and controls its response to DNA double-strand breaks. Proc Natl Acad Sci U S A. 2013;110:20982-7 pubmed publisher..Our findings highlight the multistep roles of RNF168 in signaling DNA damage. ..
- Da Sylva T, Gordon C, Wu G. A genetic approach to quantifying human in vivo mutation frequency uncovers transcription level effects. Mutat Res. 2009;670:68-73 pubmed publisher..Our genomic based methods also revealed a role for transcription levels in somatic mutation generation and/or accumulation. ..
- McIntosh E, Ager D, Gadsden M, Haynes R. Human dUTP pyrophosphatase: cDNA sequence and potential biological importance of the enzyme. Proc Natl Acad Sci U S A. 1992;89:8020-4 pubmed..We suggest that dUTPase may generally perform an essential role in DNA replication and therefore could serve as a target enzyme for the development of chemotherapeutic compounds. ..