ix Chapter I: Introduction DNA DAMAGE RESPONSE 1 DNA DAMAGE REPAIR DNA modifications 3 Repair of double stranded DNA breaks 7 DNA DAMAGE RESPONSE PATHWAYS AND CANCER The link between the FA/BRCA pathway and cancer 8 The FA/BRCA pathway DNA damage response 11 FA/BRCA proteins and DNA damage repair 14 FA/BRCA proteins and cell cycle checkpoint 17 The link between the Mismatch repair pathway and c...

Background: Single nucleotide polymorphisms in 8-oxoguanine DNA glycosylase-1 (OGG1) gene modulates DNA repair capacity and functions as one of the first lines of protective mechanisms against 8-hydroxy-2’-deoxyguanosine (8-OHdG) mutagenicity. OGG1-Cys326 gene polymorphism may decrease DNA repair function, causing oxidative stress due to higher oxidative DNA damage. The main purpose of this stu...

Poly(ADP-ribose) polymerase-1 (PARP-1) was recently identified as a platinum-DNA damage response protein. To investigate the properties of binding of PARP-1 to different platinum-DNA adducts in greater detail, biotinylated DNA probes containing a site-specific cisplatin 1,2-d(GpG) or 1,3-d(GpTpG) intrastrand cross-link or a cisplatin 5'-GC/5'-GC interstrand cross-link (ICL) were utilized in bin...

The Fanconi anemia DNA repair pathway is pivotal for the efficient repair of DNA interstrand cross-links. Here, we show that FA-defective (Fancc(-)) DT40 cells arrest in G2 phase following cross-link damage and trigger apoptosis. Strikingly, cell death was reduced in Fancc(-) cells by additional deletion of the BRCA1 tumor suppressor, resulting in elevated clonogenic survival. Increased resista...

Charging and topography evolution simulations during plasma etching of high aspect ratio line-and-space patterns reveal that electron shadowing of the sidewalls critically affects charging damage. Decreasing the degree of electron shadowing by using thinner masks decreases the potentials of the etched features with a concomitant reduction in Fowler–Nordheim tunneling currents through underlying...

The protective blood-brain barrier normally allows diffusion of small molecules such as oxygen and carbon dioxide, and transport of essential nutrients, but excludes large proteins and other blood constituents from the interstitial space of the CNS. However, head trauma, stroke, status epilepticus and other pathological conditions can all compromise the integrity of this barrier, and allow bloo...