2024年8月23日
鷺さん、加納研究員のRNA-DNA hybridに関する論文がGenes to Cellsにアクセプトされました・
Title: RNA-DNA hybrids on protein coding genes are stabilized by loss of RNase H and are associated with DNA damages during S-phase in fission yeast.
Authors: Tomoko Sagi, Daichi Sadato, Kazuto Takayasu, Hiroyuki Sasanuma, Yutaka Kanoh, Hisao Masai
本論文では、分裂酵母のRNA-DNA hybridのprofileの解析とそのDNA損傷との関連を明らかにしました。
論文はこちらから。
2024年7月26日
デンマークのGenevieve Thon教授、Groth 教授らとの共同研究により、Mrc1のヒストン分配における重要な役割を解明し、下記のCell誌に発表した。
Charlton SJ, Flury V, Kanoh Y, Genzor AV, Kollenstart L, Ao W, Brøgger P, Weisser MB, Adamus M, Alcaraz N, Delvaux de Fenffe CM, Mattiroli F, Montoya G, Masai H, Groth A, Thon G. The fork protection complex promotes parental histone recycling and epigenetic memory. Cell. 2024 Jul 26:S0092-8674(24)00777-3. doi: 10.1016/j.cell.2024.07.017. Epub ahead of print. PMID: 39094569.
Title: “Water-Soluble Mn(III)-Porphyrins with High Relaxivity and Photosensitization”
Author(s): Nemeth, Tamas; Pallier, Agnes; Çelik, Çetin; garda, zoltan; Yoshizawa-Sugata, Naoko; Masai, Hisao; Tóth, Éva; Yamakoshi, Yoko
ABSTRACT: Three water-soluble Mn(III)-porphyrin complexes with cationic pyridyl side groups bearing COOH- or OH-terminated carbon chains in the meta or para positions have been synthesized as probes for both magnetic resonance imaging (MRI) and photodynamic therapy (PDT). The complexes Mn-1, Mn-2, and Mn-3 are highly water-soluble, and their relaxivities range between 10-15 mM-1s-1, at 20-80 MHz and 298K, 2-3 times higher than that of commercial Gd(III)-based agents. The complexes containing carboxylate (Mn-2) or alcoholic (Mn-3) side chains in para position are endowed with higher relaxivities and have also shown efficient photoinduced DNA cleavage and singlet oxygen (1O2) generation. Mn-3 with stronger photoinduced DNA cleavage has also revealed stabilizing and binding activities for G4 DNA, at a similar level as the known G4 binder Mn-TMPyP4. Nevertheless, the G4-binding activity of Mn-3 was non-specific. Preliminary tests evidenced photocytotoxicity of Mn-3 on HeLa cells without significant effect in the absence of light. Altogether, these results underline the potential of such water-soluble Mn(III)-porphyrins for the development of multimodal approaches combining MRI and PDT.
2024年8月14日
Zhiying You 研究員のMCMについての総説（Assembly, activation and helicase actions of MCM）がBiology誌にアクセプトされました。これは、Peter J. Gillespie博士（Cancer Research UK Chromosome Replication)が企画したReplication Licensing and MCM2-7 functionに関する特集号です。
総説のpreprintはここからダウンロードできます。
2024年3月13日
大学院生の山﨑航輔君、笹沼博之副参事研究員の論文『Homologous recombination contributes to the repair of acetaldehyde-induced DNA damages 』がCell Cycle誌(IF 4.7)への掲載が許可されました。
この論文では、アセトアルデヒドにより誘導されるDNA損傷が、相同組換え依存的修復システムで修復されることを示しました。
Abstract
Acetaldehyde, a chemical that can cause DNA damage and contribute to cancer, is prevalently present in our environment, e.g., in alcohol, tobacco, and food. Although aldehyde potentially promotes crosslinking reactions among biological substances including DNA, RNA, and proteins, it remains unclear what types of DNA damage are caused by acetaldehyde and how they are repaired. In this study, we examined the acetaldehyde sensitivity of DNA damage-deficient cells established from the human TK6 cell line. Among the mutants, mismatch repair mutants did not show hypersensitivity to acetaldehyde, while cells deficient in base and nucleotide excision repair pathways increased their sensitivity. We found a delayed repair and hypersensitivity in homologous recombination (HR)-deficient cells but not in nonhomologous end joining-deficient cells after acetaldehyde treatment. By analyzing the formation of acetaldehyde-induced RAD51 foci, which represent HR intermediates, HR-deficient cells, but not NHEJ, exhibit delayed repair of acetaldehyde-induced DNA damages, compared with wild-type. These results suggest that acetaldehyde causes complex DNA damages that require various types of repair pathways. Interestingly, mutants deficient in TDP1 and TDP2, which are involved in the removal of protein adducts from DNA ends, exhibited hypersensitivity to acetaldehyde. The acetaldehyde sensitivity of the double mutant deficient in both TDP1 and RAD54 was similar to that of each single mutant. This epistatic relationship between TDP1 and RAD54 suggests that the removal of protein-DNA adducts generated by acetaldehyde needs to be removed for efficient repair by HR. Our study would help understand the molecular mechanism of the genotoxic and mutagenic effects of acetaldehyde.
KEY WORDS: homologous recombination, acetaldehyde, DNA-protein adducts
