scholarly journals DNA Repair and Transcription in Human Premature Aging Disorders

1998 ◽  
Vol 3 (1) ◽  
pp. 11-13 ◽  
Author(s):  
Vilhelm A. Bohr ◽  
Grigoiy Dianov ◽  
Adayabalam Balajee ◽  
Alfred May ◽  
David K. Orren
Keyword(s):  
Dna Repair ◽  
Premature Aging

DNA Repair and Transcription in Human Premature Aging Disorders

1998 ◽  
Vol 3 (1) ◽  
pp. 11-13 ◽  
Author(s):  
Vilhelm A Bohr ◽  
Grigoiy Dianov ◽  
Adayabalam Balajee ◽  
Alfred May ◽  
David K Orren
Keyword(s):  
Dna Repair ◽  
Premature Aging

Skin Abnormalities in Disorders with DNA Repair Defects, Premature Aging, and Mitochondrial Dysfunction

2021 ◽  
Author(s):  
Mansoor Hussain ◽  
Sudarshan Krishnamurthy ◽  
Jaimin Patel ◽  
Edward Kim ◽  
Beverly A. Baptiste ◽  
...  
Keyword(s):  
Dna Repair ◽  
Mitochondrial Dysfunction ◽  
Premature Aging ◽  
Skin Abnormalities

scholarly journals The ATPase Domain but Not the Acidic Region of Cockayne Syndrome Group B Gene Product Is Essential for DNA Repair

1999 ◽  
Vol 10 (11) ◽  
pp. 3583-3594 ◽  
Author(s):  
Robert M. Brosh ◽  
Adayabalam S. Balajee ◽  
Rebecca R. Selzer ◽  
Morten Sunesen ◽  
Luca Proietti De Santis ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Excision Repair ◽  
Uv Light ◽  
Genetic Disorder ◽  
Cockayne Syndrome ◽  
Premature Aging ◽  
Atpase Domain ◽  
Acidic Region

Cockayne syndrome (CS) is a human genetic disorder characterized by UV sensitivity, developmental abnormalities, and premature aging. Two of the genes involved, CSA andCSB, are required for transcription-coupled repair (TCR), a subpathway of nucleotide excision repair that removes certain lesions rapidly and efficiently from the transcribed strand of active genes. CS proteins have also been implicated in the recovery of transcription after certain types of DNA damage such as those lesions induced by UV light. In this study, site-directed mutations have been introduced to the human CSB gene to investigate the functional significance of the conserved ATPase domain and of a highly acidic region of the protein. The CSB mutant alleles were tested for genetic complementation of UV-sensitive phenotypes in the human CS-B homologue of hamster UV61. In addition, theCSB mutant alleles were tested for their ability to complement the sensitivity of UV61 cells to the carcinogen 4-nitroquinoline-1-oxide (4-NQO), which introduces bulky DNA adducts repaired by global genome repair. Point mutation of a highly conserved glutamic acid residue in ATPase motif II abolished the ability of CSB protein to complement the UV-sensitive phenotypes of survival, RNA synthesis recovery, and gene-specific repair. These data indicate that the integrity of the ATPase domain is critical for CSB function in vivo. Likewise, the CSB ATPase point mutant failed to confer cellular resistance to 4-NQO, suggesting that ATP hydrolysis is required for CSB function in a TCR-independent pathway. On the contrary, a large deletion of the acidic region of CSB protein did not impair the genetic function in the processing of either UV- or 4-NQO-induced DNA damage. Thus the acidic region of CSB is likely to be dispensable for DNA repair, whereas the ATPase domain is essential for CSB function in both TCR-dependent and -independent pathways.

scholarly journals NRMT1 knockout mice exhibit phenotypes associated with impaired DNA repair and premature aging

2015 ◽  
Vol 146-148 ◽  
pp. 42-52 ◽  
Author(s):  
Lindsay A. Bonsignore ◽  
John G. Tooley ◽  
Patrick M. Van Hoose ◽  
Eugenia Wang ◽  
Alan Cheng ◽  
...  
Keyword(s):  
Dna Repair ◽  
Knockout Mice ◽  
Premature Aging

scholarly journals Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1528
Author(s):  
Benilde García-de-Teresa ◽  
Alfredo Rodríguez ◽  
Sara Frias
Keyword(s):  
Dna Repair ◽  
Fanconi Anemia ◽  
Chromosomal Instability ◽  
Bone Marrow Failure ◽  
Chromosome Instability ◽  
Premature Aging ◽  
Dna Double Strand Breaks ◽  
Interstrand Crosslinks ◽  
Pathogenic Variants ◽  
Extreme Risk

Fanconi anemia (FA), a chromosomal instability syndrome, is caused by inherited pathogenic variants in any of 22 FANC genes, which cooperate in the FA/BRCA pathway. This pathway regulates the repair of DNA interstrand crosslinks (ICLs) through homologous recombination. In FA proper repair of ICLs is impaired and accumulation of toxic DNA double strand breaks occurs. To repair this type of DNA damage, FA cells activate alternative error-prone DNA repair pathways, which may lead to the formation of gross structural chromosome aberrations of which radial figures are the hallmark of FA, and their segregation during cell division are the origin of subsequent aberrations such as translocations, dicentrics and acentric fragments. The deficiency in DNA repair has pleiotropic consequences in the phenotype of patients with FA, including developmental alterations, bone marrow failure and an extreme risk to develop cancer. The mechanisms leading to the physical abnormalities during embryonic development have not been clearly elucidated, however FA has features of premature aging with chronic inflammation mediated by pro-inflammatory cytokines, which results in tissue attrition, selection of malignant clones and cancer onset. Moreover, chromosomal instability and cell death are not exclusive of the somatic compartment, they also affect germinal cells, as evidenced by the infertility observed in patients with FA.

scholarly journals Epigenomic maintenance through dietary intervention can facilitate DNA repair process to slow down the progress of premature aging

IUBMB Life ◽  
2016 ◽  
Vol 68 (9) ◽  
pp. 717-721 ◽  
Author(s):  
Shampa Ghosh ◽  
Jitendra Kumar Sinha ◽  
Manchala Raghunath
Keyword(s):  
Dna Repair ◽  
Dietary Intervention ◽  
Repair Process ◽  
Premature Aging

scholarly journals Boosting ATM Activity Promotes Longevity in Nematodes and Mice

2017 ◽  
Author(s):  
Minxian Qian ◽  
Zuojun Liu ◽  
Linyuan Peng ◽  
Fanbiao Meng ◽  
Xiaolong Tang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Metabolic Diseases ◽  
Premature Aging ◽  
Repair Capacity ◽  
Dna Repair Capacity ◽  
Age Related ◽  
Atm Protein ◽  
First Time

AbstractDNA damage accumulates with age1. However, whether and how robust DNA repair machinery promotes longevity is elusive. Here, we demonstrate that activation of ataxia-telangiectasia mutated (ATM) via low dose of chloroquine (CQ) promotes DNA damage clearance, rescues age-related metabolic shift, and extends lifespan in nematodes and mice. Molecularly, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation. Extra copies of Sirt6 in Atm-/- mice extend lifespan, accompanied with restored metabolic homeostasis. In a progeria mouse model with low ATM protein level and DNA repair capacity, the treatment with CQ ameliorates premature aging features and extends lifespan. Thus, our data highlights a pro-longevity role of ATM, for the first time establishing direct causal links between robust DNA repair machinery and longevity, and providing therapeutic strategy for progeria and age-related metabolic diseases.

scholarly journals Human premature aging, DNA repair and RecQ helicases

2007 ◽  
Vol 35 (22) ◽  
pp. 7527-7544 ◽  
Author(s):  
R. M. Brosh ◽  
V. A. Bohr
Keyword(s):  
Dna Repair ◽  
Premature Aging ◽  
Recq Helicases
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