RRC ID 65481
著者 Kohzaki M, Ootsuyama A, Sun L, Moritake T, Okazaki R.
タイトル Human RECQL4 represses the RAD52-mediated single-strand annealing pathway after ionizing radiation or cisplatin treatment.
ジャーナル Int J Cancer
Abstract Ionizing radiation (IR) and cisplatin are frequently used cancer treatments, although the mechanisms of error-prone DNA repair-mediated genomic instability after anticancer treatment are not fully clarified yet. RECQL4 mutations mainly in the C-terminal region of the RECQL4 gene lead to the cancer-predisposing Rothmund-Thomson syndrome, but the function of RECQL4ΔC (C-terminus deleted) in error-prone DNA repair remains unclear. We established several RECQL4ΔC cell lines and found that RECQL4ΔC cancer cells, but not RECQL4ΔC nontumorigenic cells, exhibited IR/cisplatin hypersensitivity. Notably, RECQL4ΔC cancer cells presented increased RPA2/RAD52 foci after cancer treatments. RECQL4ΔC HCT116 cells exhibited increased error-prone single-strand annealing (SSA) activity and decreased alternative end-joining activities, suggesting that RECQL4 regulates the DNA repair pathway choice at double-strand breaks. RAD52 depletion by siRNA or RAD52 inhibitors (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside [AICAR], (-)-epigallocatechin [EGC]) or a RAD52-phenylalanine 79 aptamer significantly restrained the growth of RAD52-upregulated RECQL4ΔC HCT116 cells in vitro and in mouse xenografts. Remarkably, compared to single-agent cisplatin or EGC treatment, cisplatin followed by low-concentration EGC had a significant suppressive effect on RECQL4ΔC HCT116 cell growth in vivo. Together, the regimens targeting the RAD52-mediated SSA pathway after anticancer treatment may be applicable for cancer patients with RECQL4 gene mutations.
巻・号 146(11)
ページ 3098-3113
公開日 2020-6-1
DOI 10.1002/ijc.32670
PMID 31495919
MeSH Animals Catechin / analogs & derivatives Catechin / pharmacology Cell Line, Tumor Cell Proliferation / drug effects Cisplatin / pharmacology* Cross-Linking Reagents / pharmacology DNA Breaks, Double-Stranded DNA Repair / genetics* HCT116 Cells Humans MCF-7 Cells Mice Mice, Inbred C57BL Mice, Transgenic Neoplasm Transplantation Neoplasms / genetics Neoplasms / pathology Neoplasms / therapy Rad52 DNA Repair and Recombination Protein / antagonists & inhibitors Rad52 DNA Repair and Recombination Protein / genetics Rad52 DNA Repair and Recombination Protein / metabolism* Radiation, Ionizing* RecQ Helicases / genetics* Replication Protein A / genetics Transplantation, Heterologous
IF 5.145
リソース情報
ヒト・動物細胞 HCT116(RCB2979) MCF7(RCB1904)