scholarly journals Genetic variation in the NEIL2 DNA glycosylase gene is associated with oxidative DNA damage in BRCA2 mutation carriers

Oncotarget ◽  
2017 ◽  
Vol 8 (70) ◽  
pp. 114626-114636 ◽  
Author(s):  
Carlos Benítez-Buelga ◽  
Juan Miguel Baquero ◽  
Tereza Vaclova ◽  
Victoria Fernández ◽  
Paloma Martín ◽  
...  
Keyword(s):  
Dna Damage ◽  
Genetic Variation ◽  
Oxidative Dna Damage ◽  
Brca2 Mutation ◽  
Dna Glycosylase ◽  
Mutation Carriers

scholarly journals BCR-ABL1 kinase inhibits uracil DNA glycosylase UNG2 to enhance oxidative DNA damage and stimulate genomic instability

Leukemia ◽  
2012 ◽  
Vol 27 (3) ◽  
pp. 629-634 ◽  
Author(s):  
A Slupianek ◽  
R Falinski ◽  
P Znojek ◽  
T Stoklosa ◽  
S Flis ◽  
...  
Keyword(s):  
Dna Damage ◽  
Genomic Instability ◽  
Oxidative Dna Damage ◽  
Dna Glycosylase ◽  
Uracil Dna Glycosylase

scholarly journals Aneuploidy and deregulated DNA damage response define haploinsufficiency in breast tissues of BRCA2 mutation carriers

2019 ◽  
Author(s):  
Mihriban Karaayvaz ◽  
Rebecca E Silberman ◽  
Adam Langenbucher ◽  
Srinivas Vinod Saladi ◽  
Kenneth N Ross ◽  
...  
Keyword(s):  
Dna Damage ◽  
Brca2 Mutation ◽  
Copy Number Variations ◽  
Cancer Risk Assessment ◽  
Replication Checkpoint ◽  
Mutation Carriers ◽  
Risk Patients ◽  
Breast Tissues ◽  
Lp Cells

AbstractWomen harboring heterozygous germline mutations of BRCA2 have a 50-80% risk of developing breast cancer, yet the early pathogenesis of these cancers is poorly understood. We sought to reveal early steps in BRCA2-associated carcinogenesis through analysis of sorted cell populations from freshly-isolated, non-cancerous breast tissues among a cohort of BRCA2 mutation carriers and matched controls. Single-cell whole-genome sequencing demonstrates that >25% of BRCA2 carrier (BRCA2mut/+) luminal progenitor (LP) cells exhibit sub-chromosomal copy number variations (CNVs), which are rarely observed in non-carriers. Correspondingly, primary BRCA2mut/+ breast epithelia exhibit spontaneous and replication stress-induced DNA damage together with attenuated replication checkpoint and apoptotic responses, associated with an age-associated expansion of the LP compartment in human carrier tissues. These phenotypes are not associated with loss of wild-type BRCA2. Collectively, these findings provide evidence for BRCA2 haploinsufficiency and associated DNA damage in vivo that precede histologic abnormalities. These results provide unanticipated opportunities for new cancer risk assessment and prevention strategies in high-risk patients.

scholarly journals Common Genetic Variation at BARD1 Is Not Associated with Breast Cancer Risk in BRCA1 or BRCA2 Mutation Carriers

2011 ◽  
Vol 20 (5) ◽  
pp. 1032-1038 ◽  
Author(s):  
Amanda B. Spurdle ◽  
Louise Marquart ◽  
Lesley McGuffog ◽  
Sue Healey ◽  
Olga Sinilnikova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Variation ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Brca2 Mutation ◽  
Common Genetic Variation ◽  
Mutation Carriers

scholarly journals Evidence that OGG1 Glycosylase Protects Neurons against Oxidative DNA Damage and Cell Death under Ischemic Conditions

2010 ◽  
Vol 31 (2) ◽  
pp. 680-692 ◽  
Author(s):  
Dong Liu ◽  
Deborah L Croteau ◽  
Nadja Souza-Pinto ◽  
Michael Pitta ◽  
Jingyan Tian ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cortical Neurons ◽  
Oxidative Dna Damage ◽  
Nuclear Dna ◽  
Excision Repair ◽  
Mitochondrial Fission ◽  
Metabolic Stress ◽  
Artery Occlusion ◽  
Dna Glycosylase ◽  
Base Excision

7,8-Dihydro-8-oxoguanine DNA glycosylase (OGG1) is a major DNA glycosylase involved in base-excision repair (BER) of oxidative DNA damage to nuclear and mitochondrial DNA (mtDNA). We used OGG1-deficient (OGG1−/–) mice to examine the possible roles of OGG1 in the vulnerability of neurons to ischemic and oxidative stress. After exposure of cultured neurons to oxidative and metabolic stress levels of OGG1 in the nucleus were elevated and mitochondria exhibited fragmentation and increased levels of the mitochondrial fission protein dynamin-related protein 1 (Drp1) and reduced membrane potential. Cortical neurons isolated from OGG1−/– mice were more vulnerable to oxidative insults than were OGG1+/+ neurons, and OGG1−/– mice developed larger cortical infarcts and behavioral deficits after permanent middle cerebral artery occlusion compared with OGG1+/+ mice. Accumulations of oxidative DNA base lesions (8-oxoG, FapyAde, and FapyGua) were elevated in response to ischemia in both the ipsilateral and contralateral hemispheres, and to a greater extent in the contralateral cortex of OGG1−/– mice compared with OGG1+/+ mice. Ischemia-induced elevation of 8-oxoG incision activity involved increased levels of a nuclear isoform OGG1, suggesting an adaptive response to oxidative nuclear DNA damage. Thus, OGG1 has a pivotal role in repairing oxidative damage to nuclear DNA under ischemic conditions, thereby reducing brain damage and improving functional outcome.

scholarly journals Role of a MutY DNA glycosylase in combating oxidative DNA damage in Helicobacter pylori

DNA Repair ◽  
2007 ◽  
Vol 6 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Rory Eutsey ◽  
Ge Wang ◽  
Robert J. Maier
Keyword(s):  
Dna Damage ◽  
Helicobacter Pylori ◽  
Oxidative Dna Damage ◽  
Dna Glycosylase
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