The influence of XPD, APE1, XRCC1, and NBS1 polymorphic variants on DNA repair in cells exposed to X-rays

Area of Science:

• Genetics
• Molecular Biology
• Oncology

Background:

• Genetic variations in DNA repair proteins can affect cancer predisposition.
• Understanding these polymorphisms is crucial for assessing individual cancer risk.

Purpose of the Study:

• To investigate the impact of common polymorphisms in XPD, APE1, XRCC1, and NBS1 genes on DNA repair capacity after X-irradiation in colon carcinoma patients.
• To explore the functional consequences of XPD gene variants on DNA repair and cell cycle progression.

Main Methods:

• Analysis of DNA repair and strand break levels using comet assays in lymphocytes from colon carcinoma patients.
• Genotyping of XPD (Asp312Asn, Lys751Gln), APE1 (Asp148Glu), XRCC1 (Arg399Gln), and NBS1 (Gln185Glu) polymorphisms.
• Establishment of stably-transfected HCT116 colon carcinoma cells over-expressing wild-type and variant XPD proteins.

Main Results:

• Polymorphisms in APE1 (Asp148Glu) and XPD (Asp312Asn) were associated with higher DNA incisions post-irradiation.
• The XPD Asp312Asn variant demonstrated enhanced DNA strand break repair capacity.
• Wild-type XRCC1 genotype correlated with fewer DNA breaks, while NBS1 polymorphism showed no significant effect.
• XPD variant cells exhibited increased DNA breaks, more efficient repair, and altered cell cycle dynamics post-irradiation.

Conclusions:

• Polymorphisms in DNA repair genes significantly influence DNA repair efficiency and cell proliferation.
• These genetic variations can serve as biomarkers for individual DNA repair capacity and susceptibility to carcinogens.
• The findings highlight the role of specific gene polymorphisms in modulating cellular responses to DNA damage, relevant to cancer development and prevention.