Transcription factor IIH – the protein complex with multiple functions

Mydlikova, Z; Gurský, Ján; Piršel, Miroslav

doi:10.4149/neo_2010_04_287

Cited by 10 publications

(13 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TFIIH is also a component of the RNA polymerases I–III holoenzymes where it is crucial for transcription initiation and DNA unwinding during the early elongation step. Due to its complex dynamic structure and multifunctionality TFIIH is able to coordinate transcription and DNA repair, and may also relate these processes to the cell cycle control ( Mydlikova et al, 2010 ). The recruitment of TFIIH during NER allows opening of the DNA duplex, which is performed by its key helicase subunits XPB and XPD, each of them bound to a different DNA strand.…”

Section: Dna Repair Pathways In Model and Crop Plants – Nature And Efmentioning

confidence: 99%

DNA damage and repair in plants – from models to crops

2015

View full text Add to dashboard Cite

The genomic integrity of every organism is constantly challenged by endogenous and exogenous DNA-damaging factors. Mutagenic agents cause reduced stability of plant genome and have a deleterious effect on development, and in the case of crop species lead to yield reduction. It is crucial for all organisms, including plants, to develop efficient mechanisms for maintenance of the genome integrity. DNA repair processes have been characterized in bacterial, fungal, and mammalian model systems. The description of these processes in plants, in contrast, was initiated relatively recently and has been focused largely on the model plant Arabidopsis thaliana. Consequently, our knowledge about DNA repair in plant genomes - particularly in the genomes of crop plants - is by far more limited. However, the relatively small size of the Arabidopsis genome, its rapid life cycle and availability of various transformation methods make this species an attractive model for the study of eukaryotic DNA repair mechanisms and mutagenesis. Moreover, abnormalities in DNA repair which proved to be lethal for animal models are tolerated in plant genomes, although sensitivity to DNA damaging agents is retained. Due to the high conservation of DNA repair processes and factors mediating them among eukaryotes, genes and proteins that have been identified in model species may serve to identify homologous sequences in other species, including crop plants, in which these mechanisms are poorly understood. Crop breeding programs have provided remarkable advances in food quality and yield over the last century. Although the human population is predicted to “peak” by 2050, further advances in yield will be required to feed this population. Breeding requires genetic diversity. The biological impact of any mutagenic agent used for the creation of genetic diversity depends on the chemical nature of the induced lesions and on the efficiency and accuracy of their repair. More recent targeted mutagenesis procedures also depend on host repair processes, with different pathways yielding different products. Enhanced understanding of DNA repair processes in plants will inform and accelerate the engineering of crop genomes via both traditional and targeted approaches.

show abstract

Section: Dna Repair Pathways In Model and Crop Plants – Nature And Efmentioning

confidence: 99%

DNA damage and repair in plants – from models to crops

2015

View full text Add to dashboard Cite

show abstract

“…Indeed, Tfb3 is needed for efficient neddylation of Cul3 and for neddylation and ubiquitylation of Rtt101, two yeast cullins regulating DNA-associated processes. Tfb3 is an essential subunit of the TFIIH complex, which mediates transcription initiation and is also involved in nucleotide excision repair (NER) (Mydlikova et al, 2010). Because we have not found other mutations in TFIIH subunits that affect Rtt101 modification, it is unlikely that activation of Rtt101 and Cul3 neddylation is linked to TFIIH function in transcription initiation or NER.…”

Section: Discussionmentioning

confidence: 99%

“…Tfb3 is part of TFIIH, a well characterized complex involved in transcription initiation and nucleotide excision repair (NER) (Mydlikova et al, 2010). To determine whether these functions of TFIIH are involved in Rtt101 regulation, we examined Rtt101 modification in various TFIIH mutants with impaired transcription or NER activities.…”

Section: Tfb3 Probably Regulates the Conjugation Step Of Cullin Neddymentioning

confidence: 99%

The TFIIH Subunit Tfb3 Regulates Cullin Neddylation

et al. 2011

View full text Add to dashboard Cite

Cullin proteins are scaffolds for the assembly of multisubunit ubiquitin ligases, which ubiquitylate a large number of proteins involved in widely varying cellular functions. Multiple mechanisms cooperate to regulate cullin activity, including neddylation of their C-terminal domain. Interestingly, we found that the yeast Cul4-type cullin Rtt101 is not only neddylated but also ubiquitylated, and both modifications promote Rtt101 function in vivo. Surprisingly, proper modification of Rtt101 neither correlated with catalytic activity of the RING domain of Hrt1 nor required the Nedd8 ligase Dcn1. Instead, ubiquitylation of Rtt101 was dependent on the ubiquitin-conjugating enzyme Ubc4, while efficient neddylation involves the RING domain protein Tfb3, a subunit of the transcription factor TFIIH. Tfb3 also controls Cul3 neddylation and activity in vivo, and physically interacts with Ubc4 and the Nedd8-conjugating enzyme Ubc12 and the Hrt1/Rtt101 complex. Together, these results suggest that the conserved RING domain protein Tfb3 controls activation of a subset of cullins.

show abstract

“…Finally, it has been recently shown that additional factors can be required to ensure the efficient neddylation of specific cullins. TFB3, an essential subunit of the TFIIH complex, which mediates transcription initiation and is also involved in nucleotide excision repair (NER) [29], is needed for efficient neddylation of CUL3 and for neddylation and ubiquitylation of Rtt101, two yeast cullins regulating DNA-associated processes [30].…”

Section: (Senp8mentioning

confidence: 99%

New Insights into the Mechanisms Underlying NEDD8 Structural and Functional Specificities

Santonico¹

2019

Ubiquitin Proteasome System - Current Insights Into Mechanism Cellular Regulation and Disease

View full text Add to dashboard Cite

Ubiquitin (Ub) and ubiquitin-like (Ubl) proteins are small polypeptides that are conjugated to substrates affecting their activity and stability. Cells encode "receptors" containing Ub-/Ubl-binding domains that interpret and translate each modification into appropriate cellular responses. Among the different Ubls, NEDD8, which is the ubiquitin's closest relative, retains many of the structural determinants that enable ubiquitin the ability to target proteins to degradation. Nevertheless, the direct involvement of NEDD8 conjugation to proteasome recruitment has been proved only in a few cases. To date, well-defined major NEDD8 substrates are primarily members of the cullin family, and cullin neddylation does not appear to mark these proteins for degradation. Various studies have demonstrated that selectivity between ubiquitin and NEDD8 is guaranteed by small but substantial differences. Nevertheless, several issues still need to be addressed, mainly concerning which interaction surfaces mediate NEDD8 function and what domains recognize them. Recently, two novel domains identified in KHNYN and N4BP1 proteins have shed new light on this research area. Here, I discuss some recent reports that contributed to shed light on the mechanisms underlining the discrimination between ubiquitin and NEDD8. Understanding the details of these molecular mechanisms represents a prominent facet for the identification of new therapeutic targets.

show abstract

Transcription factor IIH – the protein complex with multiple functions

Cited by 10 publications

References 20 publications

DNA damage and repair in plants – from models to crops

DNA damage and repair in plants – from models to crops

The TFIIH Subunit Tfb3 Regulates Cullin Neddylation

New Insights into the Mechanisms Underlying NEDD8 Structural and Functional Specificities

Contact Info

Product

Resources

About