Claudin (CLDN) proteins are extensively studied due to their critical role in maintaining tissue barriers and cell polarity. However, significant gaps remain in understanding the functional mechanisms Show more
Claudin (CLDN) proteins are extensively studied due to their critical role in maintaining tissue barriers and cell polarity. However, significant gaps remain in understanding the functional mechanisms of their sequence motifs and the molecular mechanisms of their interactions with other tight junction proteins. This review systematically examines the multifunctional properties of the CLDN protein family from the perspectives of sequence and structure. During evolution, CLDN family members have developed highly conserved structural features, particularly key conserved sites within the first Show less
Human Replication Protein A (RPA) was historically discovered as one of the six components needed to reconstitute simian virus 40 DNA replication from purified components. RPA is now known to be invol Show more
Human Replication Protein A (RPA) was historically discovered as one of the six components needed to reconstitute simian virus 40 DNA replication from purified components. RPA is now known to be involved in all DNA metabolism pathways that involve single-stranded DNA (ssDNA). Heterotrimeric RPA comprises several domains connected by flexible linkers and is heavily regulated by post-translational modifications (PTMs). The structure of RPA has been challenging to obtain. Various structural methods have been applied, but a complete understanding of RPA's flexible structure, its function, and how it is regulated by PTMs has yet to be obtained. This review will summarize recent literature concerning how RPA is phosphorylated in the cell cycle, the structural analysis of RPA, DNA and protein interactions involving RPA, and how PTMs regulate RPA activity and complex formation in double-strand break repair. There are many holes in our understanding of this research area. We will conclude with perspectives for future research on how RPA PTMs control double-strand break repair in the cell cycle. Show less
The deregulation of gene expression is a characteristic of cancer cells, and malignant cells require very high levels of transcription to maintain their cancerous phenotype and survive. Therefore, com Show more
The deregulation of gene expression is a characteristic of cancer cells, and malignant cells require very high levels of transcription to maintain their cancerous phenotype and survive. Therefore, components of the basal transcription machinery may be considered as targets to preferentially kill cancerous cells. TFIIH is a multisubunit basal transcription factor that also functions in nucleotide excision repair. The recent discoveries of some small molecules that interfere with TFIIH and that preferentially kill cancer cells have increased researchers' interest to elucidate the complex mechanisms by which TFIIH operates. In this review, we summarize the knowledge generated during the 25 years of TFIIH research, highlighting the recent advances in TFIIH structural and mechanistic analyses that suggest the potential of TFIIH as a target for cancer treatment. Show less