Organisms have developed several DNA repair pathways as well as DNA damage checkpoints. Although each pathway is addressed

individually, the cross talk exists between repair pathways, and there are instances in which a DNA-repair protein is involved in more than one pathway. Single nucleotide polymorphisms (SNPs) in selleck chemicals DNA repair genes may be associated with differences in the repair efficiency of DNA damage and may influence an individual’s risk of cancer. Establishing this GDC-0449 clinical trial connection, however, has been a challenge due to the complexity of interactions that affect the repair pathways [3, 4]. Increasing evidence links environmental exposures, subtle modification in DNA repair efficiency, and cancer risk [5]. The genes belonging to base excision repair (BER) pathway, such as X-ray Repair Cross Complementing Group 1 (XRCC1) have been extensively studied in the association with various human cancer [6–14]. Two major SNPs of the XRCC1 gene have been identified at codon 194 (C > T substitution at position 26304, exon 6, Arg to Trp) and 399 (G > A substitution at position 28152, exon 10, Arg to Gln). The XRCC1 Arg399Gln polymorphism is located in the area coding for a PARP binding site. PARP is a zinc-fnger containing enzyme that detects DNA strand breaks [15]. Carriers of the XRCC 1 399 Gln variant allele have been shown to have higher levels of DNA adducts [16]

and to be at greater risk for ionizing radiation sensitivity [17] and https://www.selleckchem.com/products/pifithrin-alpha.html tobacco correlated DNA damage [18–20]. The XRCC1 protein plays an important role in the maintenance of genomic stability through the both base excision and single-strand break repair by acting as a scaffold for other DNA repair proteins, such as DNA glycosylases, polymerase beta [21] and ligase III [22]. XRCC1 participates in the first step of BER by interacting with the numerous of human DNA glycosylases including hOGG1, MPG, hNTH1 and NEIL1 [23, 24]. It was found that XRCC1,

through its NTD and BRCT1 domains, has affinity to DOK2 form a covalent complex via Schiff base with AP sites. It was also reported that XRCC1 affinity was higher when the DNA carried an AP-lyase- or APE1-incised AP site [25]. This results in an acceleration of the overall repair process of abasic site, which can be used as a substrate by DNA polymerase beta. Thus, this suggests mechanism by which XRCC1, through its multiple protein-protein interactions plays essential role in the resealing of the repaired DNA strand. Head and neck squamous cell carcinoma (HNSCC) comprise about 6% of all malignant neoplasm. Overall survival is low especially in developing countries and the major risk factors of HNSCC became smoking or alcohol consumption [26]. Although the functional significance of XRCC1 polymorphism has not yet been fully elucidated, due to smoking and alcohol consumption attitude it may increase risk of head and neck cancer occurrence [27].