• Biomolecules & Therapeutics
• /
• 제31권3호
• /
• pp.340-349
• /
• 2023

Mad2B (Mad2L2), the human homolog of the yeast Rev7 protein, is a regulatory subunit of DNA polymerase ζ that shares sequence similarity with the mitotic checkpoint protein Mad2A. Previous studies on Mad2B have concluded that it is a mitotic checkpoint protein that functions by inhibiting the anaphase-promoting complex/cyclosome (APC/C). Here, we demonstrate that Mad2B is activated in response to cisplatin-induced DNA damage. Mad2B co-localizes at nuclear foci with DNA damage markers, such as proliferating cell nuclear antigen and gamma histone H2AX (γ-H2AX), following cisplatin-induced DNA damage. However, unlike Mad2A, the binding of Mad2B to Cdc20 does not inhibit the activity of APC/C in vitro. In contrast to Mad2A, Mad2B does not localize to kinetochores or binds to Cdc20 in spindle assembly checkpoint-activated cells. Loss of the Mad2B protein leads to damaged nuclei following cisplatin-induced DNA damage. Mad2B/Rev7 depletion causes the accumulation of damaged nuclei, thereby accelerating apoptosis in human cancer cells in response to cisplatin-induced DNA damage. Therefore, our results suggest that Mad2B may be a critical modulator of DNA damage response.

• 한국산업정보학회논문지
• /
• 제15권1호
• /
• pp.37-46
• /
• 2010

서픽스 트리는 데이터의 내부구조를 자세히 나타내고 선형시간 탐색이 가능한 효과적인 자료구조로서 DNA 서열분석 등에 유용하다. 그러나 서열을 서픽스 트리로 구축하는 경우 트리의 크기가 원본의 최소 30배 이상으로 커지므로 테라바이트(TB)급의 대용량 DNA 서열의 경우에 메모리상의 응용은 매우 어려운 문제점이 있다. 이에 본 논문에서는 디스크를 이용한 대용량 DNA의 서픽스 트리 응용기법을 제시한다. 이때 DNA 서열구조를 고려한 서픽스 트리 선형 탐색 특성 유지를 보장한다. 이를 검증하기 위하여 9G Byte의 유전자 단편 서열을 이용해 424G Byte의 서픽스 트리를 디스크에 구축한 다음, 임의의 질의 서열에 대해 KMP알고리즘과 비교한 결과 질의 응답시간에서 우수한 성능을 보였다.

• Bulletin of the Korean Chemical Society
• /
• 제25권7호
• /
• pp.1025-1030
• /
• 2004

A hybrid linear polymer-dendrimer block copolymer, poly(ethylene glycol)-block-poly(L-lysine) dendrimer, was synthesized and introduced to form polyionic complexes with DNA. The copolymer formed core-shell type nanoparticles with plasmid DNA. From dynamic light scattering experiments, the mean diameter of the polyplexes was observed to be 154.4 nm. The complex showed much increased water solubility compared to poly(L-lysine). The plasmid DNA in polyplexes was efficiently protected from the enzymatic digestion of DNase I. The cytotoxicity and transfection efficiency for 293 cells was measured in comparison with poly(Llysine).

• 생물정신의학
• /
• 제7권2호
• /
• pp.123-130
• /
• 2000

The development of inexpensive high throughput methods to identify individual DNA sequences is important to the future growth of medical genetics. This has become increasingly apparent as psychiatric geneticists focus more attention on the molecular basis of complex multifactorial diseases at which most of psychiatric disease is estimated. Furthermore, candidate gene approaches used in identifying disease associated genes necessitate screening large sequence blocks for changes tracking with the disease state. Even after such genes are isolated, large scale mutational analysis will often be needed for risk assessment studies to define the likely medical consequences of carrying a mutated gene. This review provide basic knowledge of up-to-date technology, cDNA microarray which enables above mentioned various research themes.

• BMB Reports
• /
• 제31권6호
• /
• pp.585-589
• /
• 1998

The herpes simplex virus type-1 (HSV-1)-encoded DNA polymerase consists of two subunits, the products of the UL30 and UL42 genes. UL30 and UL42 were coexpressed in Sf9 cells infected with recombinant baculoviruses carrying the two genes. The UL30 and UL42 gene products remained tightly associated throughout the purification, which led to a near homogeneous heterodimer composed of the DNA polymerase and UL42 protein. The DNA polymerase-UL42 protein heterodimer, purified from the recombinant baculovirus-infected Sf9 cells, showed the same high degree of processivity of deoxynucleotide polymerization as the enzyme purified from the HSV-1 infected primate cells. Like the latter, it contained a 3'-5' exonuclease activity that specifically hydrolyzes an incorrectly matched nucleotide at the 3' terminus of a primer, thereby contributing to the fidelity of DNA replication.

• Journal of Applied Biological Chemistry
• /
• 제56권1호
• /
• pp.37-42
• /
• 2013

In eukaryotes, most of the genome are transcribed, however only a small proportion of total transcripts encodes for protein, thus resulting in many of noncoding RNAs. In order to recover DNA damage including DNA double-strand breaks (DSBs) eukaryotes have evolved complex mechanisms and these are processed through coordinated mechanisms of protein sensors, transducers, and effectors including RNAs. During recent years, small RNAs have been increasingly studied and gradually considered as key regulators in various aspects of biology. Upon DNA damage, small RNAs including diRNAs (DSB induced RNA) are generated in both plant and human cell lines. Inhibition of their biogenesis has severe influence on DSB repair system.

• Molecules and Cells
• /
• 제40권2호
• /
• pp.83-89
• /
• 2017

Error-free replication and repair of DNA are pivotal to organisms for faithful transmission of their genetic information. Cells orchestrate complex signaling networks that sense and resolve DNA damage. Post-translational protein modifications by ubiquitin and ubiquitin-like proteins, including SUMO and NEDD8, are critically involved in DNA damage response (DDR) and DNA damage tolerance (DDT). The expression of interferon-stimulated gene 15 (ISG15), the first identified ubiquitin-like protein, has recently been shown to be induced under various DNA damage conditions, such as exposure to UV, camptothecin, and doxorubicin. Here we overview the recent findings on the role of ISG15 and its conjugation to target proteins (e.g., p53,$ {\Delta}Np63{\alpha}$, and PCNA) in the control of cellular responses to genotoxic stress, such as the inhibition of cell growth and tumorigenesis.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.176.2-176.2
• /
• 2003

Transcription factors (TF) can bind tightly to specific DNA lesions formed by some anticancer agents. The formation these TF:(drug-modified DNA) complex may disrupt expression of genes critical for cell survival, and it was proved to be one of biochemical mechanisms of anticancer activity. Based on this model, we have designed programmable DNA Alkylating agents that can also attract TF, especially nuclear receptors. As a model compound, we designed drug molecules, RA-mustard and Am580-mustard, that enable to bind both retinoic acid receptor (RAR) and DNA by using molecular modeling techniques, and synthesized them by connecting chlorambucil and ligand for RAR with a linker unit. (omitted)

• Journal of Radiation Protection and Research
• /
• 제20권2호
• /
• pp.71-78
• /
• 1995

본 연구에서는 유전자 손상회복에 관여하는 단백질을 이용하여 돌연변이 생성을 억제시키는 물질로서 알려진 cobaltous chloride가 유전자 손상회복에 미치는 영향을 연구하므로서 방사선으로 인한 손상방지 및 방사선 방어효과에 대한 적용가능성을 평가하였다. Cobaltous chloride가 RecA 단백질의 기능에 미치는 영향을 조사한 결과 RecA 단백질에 의한 DNA strand exchange 반웅에 있어 cobaltous chloride 처리로 RecA 단백질이 $_{ss}DNA$로 부터 SSB 단백질과 더 효과적으로 경쟁함으로써 안정된 $RecA-_{ss}DNA$ complex의 형성을 유도하고, 증가된 ATPase활성에 의한 ATP 가수분해로 손상된 DNA의 회복이 촉진될 수 있다는 사실을 입증 해주고 있다. 또한 RecA단백질은 UV에 의해 손상된 supercoiled DNA에 더 효과적으로 결합됨이 관찰되었으며 UV 선량과도 상관관계가 있음을 확인하였다. 따라서 이와 같은 연구결과들은 방사선으로 인한 유전적인 손상방지 및 방사선 방어효과에 관한 연구에 적용될 수 있을 것으로 기대된다.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
• /
• pp.312.2-312.2
• /
• 2002

The metal-ligand complex, ［Ru(phen)$_2$(dppz)]^{2＋}$ (phen = 1.10-phenanthroline, dppz = dipyrido［3.2-a:2', 3'-c］phenazine) (RuPD), was used as a spectroscopic probe for studying nucleic acid dynamics. The RuPD complex displays a long lifetime and a molecular light switch property upon DNA binding due to shielding of its dppz ligand from water. (omitted)