The Interaction between Polynucleotide Kinase Phosphatase and the DNA Repair Protein XRCC1 Is Critical for Repair of DNA Alkylation Damage and Stable Association at DNA Damage Sites

Abstract

Background: XRCC1 interacts with multiple DNA repair proteins. Results: Identification of mutant versions of XRCC1 that are defective in binding with a different single partner. Conclusion:Interaction between XRCC1 and polynucleotide kinase 3Ј-phosphatase is critical for the retention of XRCC1 at DNA damage sites and DNA damage repair. Significance: Insights into function of one of three DNA end processing factors that bind to the same region of XRCC1.

Micro-irradiation tools to visualize base excision repair and single-strand break repair

“…Della-Maria et al (14) utilized this system, without the addition of psoralen, to study the recruitment of XRCC1 and PNKP to the sites of laser-induced damage. Without psoralen to create cross-linked adducts, the authors proposed that this system generated free radical-induced SSBs in the irradiated region with no γH2AX foci detected (14).…”

“…Della-Maria et al (14) utilized this system, without the addition of psoralen, to study the recruitment of XRCC1 and PNKP to the sites of laser-induced damage. Without psoralen to create cross-linked adducts, the authors proposed that this system generated free radical-induced SSBs in the irradiated region with no γH2AX foci detected (14). Recruitment kinetics of enhanced yellow fluorescent protein (YFP) fused XRCC1 showed a longer time to peak recruitment (~18 min) and retention of XRCC1 at the damage site for more than an hour (14).…”

“…Without psoralen to create cross-linked adducts, the authors proposed that this system generated free radical-induced SSBs in the irradiated region with no γH2AX foci detected (14). Recruitment kinetics of enhanced yellow fluorescent protein (YFP) fused XRCC1 showed a longer time to peak recruitment (~18 min) and retention of XRCC1 at the damage site for more than an hour (14). While the retention appears consistent with a previous report (19), the slow accumulation of XRCC1 at the damage site is not.…”

Polymorphism of excision repair genes XPD, XRCC1, and hOGG1 in the population of the republic of Belarus and its impact on carcinogenesis

“…The three most important polymorphic variants of this gene are as follows: in codons 194 (Arg → Trp), 280 (Arg → His), and 399 (Arg → Gln) (Duell et al, 2002;Berquist et al, 2010). Polymorphism in codon 399 in c c exon 10 affects its central domain, required for the activation of base repair, leads to amino acid substitu tion of arginine to glutamine, modifying the activity of the product and increasing the sensitivity of the genome to DNA damaging factors, including alkylat ing agents (Della Maria et al, 2012). It was also found that some alleles of gene XRCC1 affect carcinogenesis (Tudek, 2007).…”

POLYMORPHISM OF EXCISION REPAIR GENES XPD, XRCC1, hOGG1 IN THE POPULATION OF THE REPUBLIC OF BELARUS AND ITS IMPACT ON CARCINOGENESIS

“…Имеется три наиболее важных полиморфных варианта этого гена: в кодонах 194 (Arg → Trp), 280 (Arg → His) и 399 (Arg → Gln) (Duell et al, 2002;Berquist et al, 2010). Полиморфизм кодона 399 в 10-м экзоне затрагивает его центральный домен, необходимый для активации репа-рации оснований, приводит к замене аминокислот арги-нина на глутамин, изменяя активность продукта и увели-чивая чувствительность генома к ДНК-повреждающим, в том числе алкилирующим, агентам (Della-Maria et al, 2012). Установлено также, что некоторые аллели гена XRCC1 влияют на канцерогенез (Tudek, 2007).…”