scholarly journals The Main Role of Human Thymine-DNA Glycosylase Is Removal of Thymine Produced by Deamination of 5-Methylcytosine and Not Removal of Ethenocytosine

2002 ◽  
Vol 278 (10) ◽  
pp. 8739-8744 ◽  
Author(s):  
Mika Abu ◽  
Timothy R. Waters
2021 ◽  
Author(s):  
Hala Ouzon-Shubeita ◽  
Lillian Feigang Schmaltz ◽  
Seongmin Lee

G:T mismatches, the major mispairs generated during DNA metabolism, are repaired in part by mismatch-specific DNA glycosylases such as methyl-CpG-binding domain 4 (MBD4) and thymine DNA glycosylase (TDG). Mismatch-specific DNA glycosylases must discriminate the mismatches against million-fold excess correct base pairs. MBD4 efficiently removes thymine opposite guanine but not opposite adenine. Previous studies have revealed that the substrate thymine is flipped out and enters the catalytic site of the enzyme, while the estranged guanine is stabilized by Arg468 of MBD4. To gain further insights into mismatch discrimination mechanism of MBD4, we assessed the glycosylase activity of MBD4 toward various base pairs. In addition, we determined a crystal structure of MBD4 bound to T:O6-methylguanine-containing DNA, which suggests the O6 and N2 of purine and the O4 of pyrimidine are required to be a substrate for MBD4. To understand the role of the Arg468 finger in catalysis, we evaluated the glycosylase activity of MBD4 mutants, which revealed the guanidinium moiety of Arg468 may play an important role in catalysis. D560N/R468K MBD4 bound to T:G mismatched DNA shows that the side chain amine moiety of the Lys stabilizes the flipped-out thymine by a water-mediated phosphate pinching, while the backbone carbonyl oxygen of the Lys engages in hydrogen bonds with N2 of the estranged guanine. Comparison of various DNA glycosylase structures implies the guanidinium and amine moieties of Arg and Lys, respectively, may involve in discriminating between substrate mismatches and nonsubstrate base pairs.


Author(s):  
Hideo Hayashi ◽  
Yoshikazu Hirai ◽  
John T. Penniston

Spectrin is a membrane associated protein most of which properties have been tentatively elucidated. A main role of the protein has been assumed to give a supporting structure to inside of the membrane. As reported previously, however, the isolated spectrin molecule underwent self assemble to form such as fibrous, meshwork, dispersed or aggregated arrangements depending upon the buffer suspended and was suggested to play an active role in the membrane conformational changes. In this study, the role of spectrin and actin was examined in terms of the molecular arrangements on the erythrocyte membrane surface with correlation to the functional states of the ghosts.Human erythrocyte ghosts were prepared from either freshly drawn or stocked bank blood by the method of Dodge et al with a slight modification as described before. Anti-spectrin antibody was raised against rabbit by injection of purified spectrin and partially purified.


2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.


2018 ◽  
Vol 5 (1) ◽  
pp. 93-115
Author(s):  
Miloš Stamenković

SummarySports photography undoubtedly has a significant place in sports press and publicism. It’s main and primary role is to present sports to the readers as art, which it is. Sport is characterized by dynamic and varied movements, and the main role of sports photography is reflected in the fact that it is in this way that sport shows its essence. Having in mind that photography tells more than a thousand words it sends a clear message to the reader as well to people who are informed about events via sports portals. Sports photography is a multidimensional art for many reasons. When we say “multi”, it primarily refers to a wider range that sports photography has to offer, which means sports photography is not only directed at presenting athletes on the move and the main actors who contribute to achieving the results by their engagement – it also has the role of sports “psychophotography” which is an analysis and capture of the emotional reaction of an athlete after winning or losing from the opposing team.


2020 ◽  
Vol 26 (6) ◽  
pp. 1283-1296
Author(s):  
K.A. Omarieva ◽  
P.G. Isaeva

Subject. The article addresses problems and prospects for the banking supervision development in the Russian Federation under modern conditions. Objectives. We review the essence and methods of organization of the banking supervision, and identify the main problems and prospects for its development. Methods. To provide valid, reliable and reasoned recommendations, we apply normative and integrated approaches to the study of the banking supervision effectiveness in the current circumstances. Results. The paper investigates main problems and development prospects for the Russian banking supervision. The essential importance of supervision comes from the main role of the banking system in maintaining accounts of economic entities and making settlements. Even minor failures or delays in operations can lead to negative outcomes and disastrous consequences for the entire monetary system and the national economy. Therefore, we highlight issues that require attention, and make proposals for further development of the banking supervision. Conclusions. In the context of dynamically developing economy, the banking practice is becoming more complex. As a result, there is a need for new financial instruments that can reduce risks, increase the speed and efficiency of operations and document flow, and help achieve the world levels of introduced standards.


Author(s):  
Shamim Mushtaq

Uninhibited proliferation and abnormal cell cycle regulation are the hallmarks of cancer. The main role of cyclin dependent kinases is to regulate the cell cycle and cell proliferation. These protein kinases are frequently down regulated or up regulated in various cancers. Two CDK family members, CDK 11 and 12, have contradicting views about their roles in different cancers. For example, one study suggests that the CDK 11 isoforms, p58, inhibits growth of breast cancer whereas, the CDK 11 isoform, p110, is highly expressed in breast tumor. Studies regarding CDK 12 show variation of opinion towards different parts of the body, however there is a consensus that upregulation of cdk12 increases the risk of breast cancer. Hence, CDK 11 and CDK 12 need to be analyzed to confirm their mechanism and their role regarding therapeutics, prognostic value, and ethnicity in cancer. This article gives an outline on both CDKs of information known up to date from Medline, PubMed, Google Scholar and Web of Science search engines, which were explored and thirty relevant researches were finalized.


Sign in / Sign up

Export Citation Format

Share Document