RRC ID 3806
Author Wang Y, Liu X, Matsuda A, Plunkett W.
Title Repair of 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine-induced DNA single-strand breaks by transcription-coupled nucleotide excision repair.
Journal Cancer Res
Abstract The cytosine nucleoside analogue 2'-C-cyano-2'-deoxy-1-beta-d-arabino-pentofuranosylcytosine (CNDAC) causes DNA single-strand breaks after its incorporation into DNA. This investigation sought to determine if DNA excision repair pathways were activated to repair this damage. Neither the base excision repair nor the mismatch repair pathway seemed to be involved. Cells deficient in the CSB protein, which initiates transcription-coupled nucleotide excision repair (NER) pathway (TC-NER), exhibited increased clonogenic sensitivity to CNDAC, whereas cells deficient in XPC, which initiates global genome NER, were slightly resistant relative to wild-type cells. The cells lacking either helicase XPB, which unwinds 5' of the lesion, or endonuclease XPF, which incises 5' to a lesion, exhibited increased clonogenic sensitivity to CNDAC, as did cells lacking the XPF partner protein ERCC1. This sensitization was independent of p53 function. Repletion of XPF restored sensitivity comparable with the wild type. In contrast, cells lacking either XPD, the 3'-helicase, or the 3'-endonuclease XPG were equally as sensitive as wild-type cells. In comparison, cells deficient in XPF were not sensitized to other cytosine nucleoside analogues, troxacitabine and cytarabine. Thus, the single-strand nick caused by CNDAC is recognized and, in part, repaired by the TC-NER pathway. NER proteins that function in the 5' direction relative to the UV-induced lesion also participate in the repair of the CNDAC-induced nick, in contrast to proteins that process on the 3' side of the lesion.
Volume 68(10)
Pages 3881-9
Published 2008-5-15
DOI 10.1158/0008-5472.CAN-07-6885
PII 68/10/3881
PMID 18483273
MeSH Animals Antineoplastic Agents / pharmacology CHO Cells Cell Line, Tumor Cricetinae Cricetulus Cytarabine / analogs & derivatives* Cytarabine / pharmacology Cytosine / analogs & derivatives Cytosine / chemistry Cytosine / pharmacology DNA Damage DNA Repair* Dioxolanes / pharmacology HeLa Cells Humans Mice Transcription, Genetic* Tumor Suppressor Protein p53 / metabolism
IF 9.727
Times Cited 17
DNA material pcDNA3-XPF (RDB01785)