Search results for "Repair"

Mitochondrial Oxidative Stress, Mitochondrial DNA Damage and Their Role in Age-Related Vascular Dysfunction

2015

The prevalence of cardiovascular diseases is significantly increased in the older population. Risk factors and predictors of future cardiovascular events such as hypertension, atherosclerosis, or diabetes are observed with higher frequency in elderly individuals. A major determinant of vascular aging is endothelial dysfunction, characterized by impaired endothelium-dependent signaling processes. Increased production of reactive oxygen species (ROS) leads to oxidative stress, loss of nitric oxide (•NO) signaling, loss of endothelial barrier function and infiltration of leukocytes to the vascular wall, explaining the low-grade inflammation characteristic for the aged vasculature. We here disc…

Combined QM/MM investigation on the light-driven electron-induced repair of the (6-4) thymine dimer catalyzed by DNA photolyase.

2013

The (6-4) photolyases are blue-light-activated enzymes that selectively bind to DNA and initiate splitting of mutagenic thymine (6-4) thymine photoproducts (T(6-4)T-PP) via photoinduced electron transfer from flavin adenine dinucleotide anion (FADH(-)) to the lesion triggering repair. In the present work, the repair mechanism after the initial electron transfer and the effect of the protein/DNA environment are investigated theoretically by means of hybrid quantum mechanical/molecular mechanical (QM/MM) simulations using X-ray structure of the enzyme-DNA complex. By comparison of three previously proposed repair mechanisms, we found that the lowest activation free energy is required for the …

Photoinduced DNA Lesions in Dormant Bacteria: The Peculiar Route Leading to Spore Photoproducts Characterized by Multiscale Molecular Dynamics

2020

International audience; Some bacterial species enter a dormant state in the form of spores to resist to unfavorable external conditions. Spores are resistant to a wide series of stress agents, including UV radiation, and can last for tens to hundreds of years. Due to the suspension of biological functions, such as DNA repair, they accumulate DNA damage upon exposure to UV radiation. Differently from active organisms, the most common DNA photoproducts in spores are not cyclobutane pyrimidine dimers, but rather the so‐called spore photoproducts. This noncanonical photochemistry results from the dry state of DNA and its binding to small, acid‐soluble proteins that drastically modify the struct…

PARP inhibitor resistance induces massive genome alterations responsible of the acquisition of multidrug resistance in DNA damage repair-deficient pa…

2020

Effect of mismatch repair on the mutation rate of bacteriophage ϕX174

2015

Viral mutation rates vary widely in nature, yet the mechanistic and evolutionary determinants of this variability remain unclear. Small DNA viruses mutate orders of magnitude faster than their hosts despite using host-encoded polymerases for replication, which suggests these viruses may avoid post-replicative repair. Supporting this, the genome of bacteriophage ϕX174 is completely devoid of GATC sequence motifs, which are required for methyl-directed mismatch repair in Escherichia coli . Here, we show that restoration of the randomly expected number of GATC sites leads to an eightfold reduction in the rate of spontaneous mutation of the phage, without severely impairing its replicative capa…

Extrathoracic Lengthening (Kimura Technique)

2021

Treatment of congenital long gap esophageal atresia is extremely challenging. Cases are rare, variable, and oftentimes complex. Possible treatment options include delayed primary repair after initial gastrostomy, gastric transposition, intestinal interpositions, traction procedures, myotomy, and gastric tube techniques. Treatment strategies often consist of variations and combinations of different approaches.

Invagination of the Sphenoid Sinus Mucosa after Endoscopic Endonasal Transsphenoidal Approach and Its Significance

2016

Objective To describe the clinical features of invagination of the sphenoid sinus mucosa (ISM) and compare them with other similar cases using a visual analog scale (VAS) to assess the various nasal symptoms and to discuss its clinical significance and means of prevention. Study design Retrospective chart review at a tertiary referral center. Methods Between 2010 and 2015, 8 patients who had undergone EETSA surgery displayed postoperative ISM. The comparison group consisted of 147 patients who underwent the same surgical procedures and were diagnosed with the same diseases. Pre- or postoperative paranasal sinus computed tomography (PNS CT) and VAS were performed and subsequently analyzed. R…

Interplay of DNA repair and damage signaling in genotoxin-induced apoptosis and necrosis

2009

Investigating the use of primary adult subventricular zone neural precursor cells for neuronal replacement therapies

2002

With the relatively recent discovery that neurogenesis persists throughout life in restricted regions of the adult mammalian brain, including those of human beings, there has been great interest in the use of adult-derived neural stem cells for neuronal replacement. There are many great hurdles that must be overcome in order for such replacement strategies to succeed. In this review, we outline some of these hurdles and discuss recent experiments that investigate the potential of using neural precursor cells found in the subventricular zone of the adult brain for brain repair.

Role of MTHFR (677, 1298) haplotype in the risk of developing secondary leukemia after treatment of breast cancer and hematological malignancies

2007

Therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) is a malignancy occurring after exposure to chemotherapy and/or radiotherapy. Polymorphisms involved in chemotherapy/radiotherapy response genes could be related to an increased risk of developing this neoplasia. We have studied 11 polymorphisms in genes of drug detoxification pathways (NQO1, glutathione S-transferase pi) and DNA repair xeroderma pigmentosum, complementation group (3) (XPC(3), X-ray repair cross complementing protein (1)), Nijmegen breakage syndrome (1), excision repair cross-complementing rodent repair deficiency, complementation group (5) and X-ray repair cross complementing protein (3) and in the methy…