Telomeres protect DNA ends of linear eukaryotic chromosomes from degradation and fusion, and ensure complete replication of the terminal DNA through recruitment of telomerase. The regulation of telomerase is a critical area of telomere research and includes cis regulation by the shelterin complex in mammals and fission yeast. We have identified a key component of this regulatory pathway as the SUMOylation [the covalent attachment of a small ubiquitin-like modifier (SUMO) to target proteins] of a shelterin subunit in fission yeast. SUMOylation is known to be involved in the negative regulation of telomere extension by telomerase; however, how SUMOylation limits the action of telomerase was unknown until now. We show that SUMOylation of the shelterin subunit TPP1 homolog in Schizosaccharomyces pombe (Tpz1) on lysine 242 is important for telomere length homeostasis. Furthermore, we establish that Tpz1 SUMOylation prevents telomerase accumulation at telomeres by promoting recruitment of Stn1-Ten1 to telomeres. Our findings provide major mechanistic insights into how the SUMOylation pathway collaborates with shelterin and Stn1-Ten1 complexes to regulate telomere length.CST complex | DNA replication | S-phase | cell cycle T elomeres protect DNA ends of linear eukaryotic chromosomes from degradation and fusion, and ensure replication of the terminal DNA (1, 2). In most eukaryotes, telomere length is maintained predominantly by telomerase, a specialized reverse transcriptase that adds telomeric DNA to the 3′ ends of chromosomes. In addition, a DNA homologous recombination (HR)-dependent mechanism, known as the alternative lengthening of telomeres (ALT) pathway, may contribute to telomere maintenance (3). Given the significant contribution of dysfunctional telomeres to genome instability, cancer development, and aging (4), understanding how telomere maintenance and the cellular response to telomere dysfunction is important. Maintenance of stable telomere length requires a balance of positive and negative regulators of telomerase. The molecular details of such regulation are not completely understood, however, and further investigation of how telomeres ensure genomic integrity is needed.Telomere regulation is largely mediated by the shelterin complex specifically bound to telomeric repeats (2). In mammalian cells, the shelterin complex (composed of TRF1, TRF2, RAP1, TIN2, TPP1, and POT1) plays critical roles in (i) regulating telomerase recruitment, (ii) preventing full-scale activation of DNA damage checkpoint responses by checkpoint kinases ATM and ATR, (iii) preventing DNA resection, and (iv) preventing telomere rearrangement and fusion by HR, classical nonhomologous end-joining (NHEJ), or alternative NHEJ (2, 5, 6).Fission yeast Schizosaccharomyces pombe serves as an attractive model system for studying telomere regulation, because it uses a complex that closely resembles the mammalian shelterin (7). Fission yeast shelterin is composed of Taz1 (an ortholog of TRF1 and TRF2), Rap1, Poz1 (a possible analog of TIN2), TPP...

The MCM2–7 hetero-hexamer is the replicative DNA helicase that plays a central role in eukaryotic DNA replication. In proliferating cells, the expression level of the MCM2–7 hexamer is kept high, which safeguards the integrity of the genome. However, how the MCM2–7 hexamer is assembled in living cells remains unknown. Here, we revealed that the MCM-binding protein (MCMBP) plays a critical role in the assembly of this hexamer in human cells. MCMBP associates with MCM3 which is essential for maintaining the level of the MCM2–7 hexamer. Acute depletion of MCMBP demonstrated that it contributes to MCM2–7 assembly using nascent MCM3. Cells depleted of MCMBP gradually ceased to proliferate because of reduced replication licensing. Under this condition, p53-positive cells exhibited arrest in the G1 phase, whereas p53-null cells entered the S phase and lost their viability because of the accumulation of DNA damage, suggesting that MCMBP is a potential target for killing p53-deficient cancers.

Background: MCM-BP is a novel binding partner of the MCM complex; the mechanisms by which MCM-BP functions and associates with MCM complexes are not well understood. Results: Genetic analysis showed that mcb1 ts mutants exercise defective regulation of prereplicative MCM complex formation during DNA replication. Conclusion:Mcb1 regulates MCM function during prereplicative complex formation in DNA replication. Significance: This study presents the first evidence of MCM-BP function during prereplicative complex formation.

Photodynamic therapy (PDT) is a considerably new kind of photochemotherapeutic treatment in medical field. It combines the use of three components, which are a photosensitizer, light and oxygen. Photosensitizer is a compound activated by light. The application can be oral, topical or intravenous. It usually member of porphyrin group with ampiphilic characteristics. Photosensitizer can be of generation I, II or III, each generation step develops more specificity, selectivity and deeper tissue application. This review will discuss photosensitizer development consecutively, with its benefit and lackness. The light used is usually on red region, while the oxygen is involved in reactive oxygen species generation. Its mechanism action can go through either in type I or type II reaction. This kind of therapy is usually being used in oncology, especially in superficial and in-lining cancers, dermatology and ophthalmology field. This therapy can be safely given to patients with complication and has distinct advantages compare with other treatment such as chemotherapy and surgery. It also considerably has lesser side effects and risks. Broader application is being developed through various experiments and photosensitizer modification.   Keywords: light spectrum, photoactivation, photodynamic therapy, photosensitizer

Soybean mosaic virus (SMV) is one of the viruses, which can reduce the quality and the amount of soybean [Glycine max (L.) Merr.] production. Control of the disease by planting resistant varieties to SMV is considered as the best method and environmentally safe. The aim of this research was to identify resistance to SMV with high yield on F7 soybean lines. Each of 56 best F7 lines was obtained from selection of F2 to F6 lines using the modified bulk method. Every breeding line was planted together with its parents in one block. Each line was grown in a 2 m × 3 m plot at a 40 cm × 15 cm plant spacing. The trial was set in a randomized complete block design with three replications. Resistance to SMV-T isolate was analyzed by symptom observation and serological detection using Double antibody sandwich enzyme-linked immunosorbent assay (DAS ELISA). The symptoms varied from mild, mosaic, necrotic and symptomless reactions. Out of the 56 soybean lines, 54 soybean lines reacted negative. Titre of virus showed absorbance values lower than two lines were susceptible, i.e. (1) W/PI 200485-7-8; (2) GK/Mlg 3288-7-11. The highest yield (2.59 t/ha) with the lowest disease severity category achieved by lines (GK/PI 200485-7-8). There were significant differences in disease severity and seed yields between Wilis and Gepak Kuning varieties as parents with high yield potential in breeding line. The path analysis indicated that the number of pods per plant directly affected the seed yields.

The MCM2-7 hetero-hexamer is the replicative DNA helicase that plays a central role in eukaryotic DNA replication. In proliferating cells, the expression level of the MCM2-7 hexamer is kept high, which safeguards the integrity of the genome. However, how the MCM2-7 hexamer is assembled in living cells remains unknown. Here, we revealed that the MCM-binding protein (MCMBP) plays a critical role in the assembly of this hexamer in human cells. MCMBP associates with MCM3 which is essential for maintaining the level of the MCM2-7 hexamer. Acute depletion of MCMBP demonstrated that it contributes to MCM2-7 assembly using nascent MCM3. Cells depleted of MCMBP gradually ceased to proliferate because of reduced replication licensing. Under this condition, p53-positive cells exhibited arrest in the G1 phase, whereas p53-null cells entered the S phase and lost their viability because of the accumulation of DNA damage, suggesting that MCMBP is a potential target for killing p53-deficient cancers.

Small Ubiquitin-related MOdifier (SUMO) proteins can be found in many organisms, including A. thaliana, which possesses 9 SUMO genes. SUMO binds to various target proteins in a reversible reaction called SUMOylation. SUMOylation participates in transcription, chromosome organization, proteins localizations and stress responses. Our study showed that RIN13 (RPM1-Interacting13/At2g20310) is a target of SUMOylation, which was initially found by interaction between this protein and AtSCE1a (E2). Recent report showed that overexpression of RIN13 enhanced the resistance to pathogen without inducing hypersensitive response. However, the molecular interaction between RIN13 and SUMO proteins and its significance have not been studied yet. Thus, our study aimed to characterize the Interaction between RIN13 and SUMO proteins in A. thaliana. The result showed an isoform-specific SUMOylation between RIN13 and SUMO proteins. RIN13 is SUMOylated by SUMO1, 2, 3, and 5. Though expressed ubiquitously in A.thaliana, fluorescence microscopy showed that RIN13 localizes subcellularly in the nuclear body. Moreover, complete abolishment of SUMOylation with inactive E2 suggests the exclusion of RIN13 from nuclear body. These results showed that SUMOylation affected RIN13 localization, and indirectly influenced its interaction to other proteins and putative function. This paper presents evidence of RIN13 SUMOylation. Furthermore, RIN13 function in pathogenic resistance is shown to be supported by SUMOylation. Thus, this study enhanced the understanding of SUMO in plants and served as reference to molecular studies concerning post-translational modification of SUMO. How to Cite

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