Shin Ki-Hyuk, Kang Mo K, Kim Reuben H, Kameta Ayako, Baluda Marcel A, Park No-Hee
UCLA School of Dentistry, Los Angeles, CA 90095-1668, USA.
Int J Mol Med. 2006 May;17(5):917-24.
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.
在人类细胞中，DNA双链断裂（DSB）主要通过DNA末端连接（EJ）过程进行修复，因此，异常的DNA EJ活性会导致突变积累和/或非整倍体形成，从而导致细胞的遗传不稳定。由于遗传不稳定是癌细胞的标志，我们研究了正常、非恶性永生化和恶性人类上皮细胞的DNA EJ活性，以探讨DNA EJ与致癌作用之间的关联。我们发现，与正常人口腔角质形成细胞（NHOK）相比，非恶性永生化人类口腔角质形成细胞（HOK-16B）和人类头颈部鳞状细胞癌（HNSCC）细胞中精确（无错误）的DNA EJ活性显著降低。此外，由于这些细胞中的微同源性介导和非微同源性介导的末端连接活性，仅在HOK-16B和HNSCC细胞中检测到异常的DNA EJ活性。这些数据表明，异常的DNA EJ活性可能部分导致遗传不稳定和致癌转化。
