Overview of xeroderma pigmentosum proteins architecture, mutations and post-translational modifications

Feltes, Bruno César; Bonatto, Diego

doi:10.1016/j.mrrev.2014.12.002

Cited by 47 publications

(41 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the presence of SIRT1 inhibitor, RASSF1A is no longer able to promote XPA deacetylation. XPG is acetylated by p300 acetyltransferase and its homolog CREB-binding protein (CBP) in vivo, which facilitates XPG accumulation at sites of DNA damage in a PCNA-p21 dependent manner [85,98]. Knockdown of both p300/CBP by RNAi or by chemical inhibition with curcumin significantly reduces XPG acetylation, and a concomitant accumulation of the protein at DNA damage sites is observed.…”

Section: Posttranslational Regulation Of Ner Factorsmentioning

confidence: 99%

Transcriptional and Posttranslational Regulation of Nucleotide Excision Repair: The Guardian of the Genome against Ultraviolet Radiation

Park

Kang

2016

IJMS

View full text Add to dashboard Cite

Ultraviolet (UV) radiation from sunlight represents a constant threat to genome stability by generating modified DNA bases such as cyclobutane pyrimidine dimers (CPD) and pyrimidine-pyrimidone (6-4) photoproducts (6-4PP). If unrepaired, these lesions can have deleterious effects, including skin cancer. Mammalian cells are able to neutralize UV-induced photolesions through nucleotide excision repair (NER). The NER pathway has multiple components including seven xeroderma pigmentosum (XP) proteins (XPA to XPG) and numerous auxiliary factors, including ataxia telangiectasia and Rad3-related (ATR) protein kinase and RCC1 like domain (RLD) and homologous to the E6-AP carboxyl terminus (HECT) domain containing E3 ubiquitin protein ligase 2 (HERC2). In this review we highlight recent data on the transcriptional and posttranslational regulation of NER activity.

show abstract

Section: Posttranslational Regulation Of Ner Factorsmentioning

confidence: 99%

Transcriptional and Posttranslational Regulation of Nucleotide Excision Repair: The Guardian of the Genome against Ultraviolet Radiation

Park

Kang

2016

IJMS

View full text Add to dashboard Cite

show abstract

“…In both pathways, XPA is recruited to the damage site by the transcription factor II H (TFIIH) complex that is responsible for unwinding double-stranded DNA around the damaged nucleotide creating the NER bubble. XPA is generally understood to function in damage-verification and assembly of NER incision complexes 1,25-27 . XPA is recruited at the same time, and functions in coordination with, the eukaryotic ssDNA binding protein replication protein A (RPA).…”

Section: Introductionmentioning

confidence: 99%

XPA: A key scaffold for human nucleotide excision repair

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Mutations in xeroderma pigmentosum proteins are often related to different cancer types and are responsible for the disease xeroderma pigmentosum, an autosomal recessive skin disorder characterized by extreme UV sensitivity and an increased incidence of sunlight-induced skin cancers. Xeroderma pigmentosum type G (XPG) proteins (also known as excision repair cross-complementation group 5) belong to the FEN-1 family of structure-specific nucleases and play an essential role in both NER pathways, transcription-coupled repair and global genome repair [1,[4][5][6][7][8]. Mutations in XPG proteins may also lead to the Cockayne syndrome, associated with severe developmental retardation, dwarfism and neurological abnormalities [9,10].…”

Section: Introductionmentioning

confidence: 99%

Structural and Calorimetric Studies Demonstrate that Xeroderma Pigmentosum Type G (XPG) Can Be Imported to the Nucleus by a Classical Nuclear Import Pathway via a Monopartite NLS Sequence

Barros

Takeda

Dreyer

et al. 2016

Journal of Molecular Biology

View full text Add to dashboard Cite

Xeroderma pigmentosum type G (XPG) proteins are involved in DNA lesion recognition and promotion of nucleotide excision repair. Specific mutations in these proteins may lead to Cockayne syndrome, in which the patients may display severe developmental retardation and neurological abnormalities. No structural information is available for their spacer region or the C-terminal domain, which are important, respectively, for specific nucleotide excision repair activity and substrate specificity, as well as nuclear translocation. Immunofluorescence studies suggested two specific regions of the XPG C-terminus as potential bipartite nuclear localization sequences, which would be responsible for its translocation to the nucleus by the classical nuclear import pathway mediated by the importin-α (Impα). Thus, in order to test these hypotheses and gain insight into the structural basis for the nuclear import process for the XPG protein, we solved the crystal structures of complexes formed by the Impα and peptides corresponding to both putative nuclear localization signal (NLS) sequences (XPG1 and XPG2) and performed isothermal titration calorimetry assays to determine their binding affinities. Structural experiments confirm the binding of both NLS peptides to Impα but, unexpectedly, they bind to the receptor as monopartite NLSs. The isothermal titration calorimetry assays demonstrated that XPG1 and XPG2 peptides bind to two separate binding sites, but with high affinity to the major NLS-binding site of the Impα, resembling classical monopartite SV40 TAg NLS. The results lead to insights about what distinguishes monopartite and bipartite NLSs, as well as the differential roles of XPG1 and XPG2 NLSs in the nuclear localization of XPG.

show abstract

Overview of xeroderma pigmentosum proteins architecture, mutations and post-translational modifications

Cited by 47 publications

References 116 publications

Transcriptional and Posttranslational Regulation of Nucleotide Excision Repair: The Guardian of the Genome against Ultraviolet Radiation

Transcriptional and Posttranslational Regulation of Nucleotide Excision Repair: The Guardian of the Genome against Ultraviolet Radiation

XPA: A key scaffold for human nucleotide excision repair

Structural and Calorimetric Studies Demonstrate that Xeroderma Pigmentosum Type G (XPG) Can Be Imported to the Nucleus by a Classical Nuclear Import Pathway via a Monopartite NLS Sequence

Contact Info

Product

Resources

About