Abnormal DNA end-joining activity in human head and neck cancer.
In human cells, DNA double-strand breaks (DSBs) are repaired primarily by the DNA end-joining (EJ) process and thus, abnormal DNA EJ activities lead to an accumulation of mutations and/or aneuploidy, resulting in genetic instability of cells. Since genetic instability is the hallmark of cancer cells, we studied the DNA EJ activities of normal, non-malignant immortalized and malignant human epithelial cells to investigate the association between DNA EJ and carcinogenesis. We found a significant diminution of precise (error-free) DNA EJ activities in non-malignant immortalized human oral keratinocytes (HOK-16B) and human head and neck squamous cell carcinoma (HNSCC) cells compared to that in normal human oral keratinocytes (NHOK). Moreover, abnormal DNA EJ activities were detected exclusively in HOK-16B and HNSCC cells due to microhomology-mediated and non-microhomology-mediated end-joining activities in these cells. These data indicated that aberrant DNA EJ activity may be partly responsible for genetic instability and oncogenic transformation.
Shin
Ki-Hyuk
KH
UCLA School of Dentistry, Los Angeles, CA 90095-1668, USA.
Kang
Mo K
MK
Kim
Reuben H
RH
Kameta
Ayako
A
Baluda
Marcel A
MA
Park
No-Hee
NH
D001483:Base Sequence; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral / Q000235:genetics; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication / Q000235:genetics; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology; D052162:Human papillomavirus 16 / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014162:Transfection
D004273:DNA, Neoplasm; D011993:Recombinant Fusion Proteins; D008156:Luciferases