Helicase-like transcription factor confers radiation resistance in cervical cancer through enhancing the DNA damage repair capacity.
Helicase-like transcription factor (HLTF) is a member of the SWI/SNF (mating type switching/sucrose non-fermenting) family of ATPases/helicases and also has a RING-finger motif characteristic of ubiquitin ligase proteins. These features have led to suggestions that HLTF functions like yeast Rad5, which promotes replication through DNA lesions via a post-replication repair pathway. However, the function of HLTF in higher eukaryotes is still unknown. Herein, we found the overexpression of HLTF in radiation recurrent human uterine cervical carcinoma tissues when compared to disease free survived patients tissues. In this study, we used RNA interference techniques to investigate the potential function of HLTF in cervical cancer cell line HeLa and found that the cell proliferation was reduced by knockdown (KD) of HLTF. A host-cell reactivation assay showed that the capacity for repair to DNA damage induced by X-ray irradiation was reduced in HLTF KD cells. X-rays also increased apoptosis in HLTF KD cells. These results suggest that HLTF is involved in DNA repair and apoptosis in cancer cells, which might represent a target for gene therapies of human cancer.
Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju 361-763, Republic of Korea.
SungHwan
S
Cho
Senthilkumar
S
Cinghu
Jae-Ran
JR
Yu
Woo-Yoon
WY
Park
D017209:Apoptosis; D049109:Cell Proliferation; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000032:analysis / Q000502:physiology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance; D014157:Transcription Factors / Q000032:analysis / Q000502:physiology*; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000532:radiotherapy*
D004268:DNA-Binding Proteins; C100023:HLTF protein, human; D034741:RNA, Small Interfering; D014157:Transcription Factors