This study reveals the molecular mechanism by which the nucleotide excision repair protein DDB2 prioritises excision of UV-induced DNA lesions in the nucleosome landscape

Carell, Thomas

Fei, Jia

Glas, Andreas

Kaczmarek, Nina

Luch, Andreas

Naegeli, Hanspeter

English

PubMed

Fei Jia

Kaczmarek Nina

Luch Andreas

Glas Andreas

Carell Thomas

Naegeli Hanspeter

Public Library of Science (PLOS)

Regulation of Nucleotide Excision Repair by UV-DDB: Prioritization of Damage Recognition to Internucleosomal DNA

How tightly packed chromatin is thoroughly inspected for DNA damage is one of the fundamental unanswered questions in biology. In particular, the effective excision of carcinogenic lesions caused by the ultraviolet (UV) radiation of sunlight depends on UV-damaged DNA-binding protein (UV-DDB), but the mechanism by which this DDB1-DDB2 heterodimer stimulates DNA repair remained enigmatic. We hypothesized that a distinctive function of this unique sensor is to coordinate damage recognition in the nucleosome repeat landscape of chromatin. Therefore, the nucleosomes of human cells have been dissected by micrococcal nuclease, thus revealing, to our knowledge for the first time, that UV-DDB associates preferentially with lesions in hypersensitive, hence, highly accessible internucleosomal sites joining the core particles. Surprisingly, the accompanying CUL4A ubiquitin ligase activity is necessary to retain the xeroderma pigmentosum group C (XPC) partner at such internucleosomal repair hotspots that undergo very fast excision kinetics. This CUL4A complex thereby counteracts an unexpected affinity of XPC for core particles that are less permissive than hypersensitive sites to downstream repair subunits. That UV-DDB also adopts a ubiquitin-independent function is evidenced by domain mapping and in situ protein dynamics studies, revealing direct but transient interactions that promote a thermodynamically unfavorable β-hairpin insertion of XPC into substrate DNA. We conclude that the evolutionary advent of UV-DDB correlates with the need for a spatiotemporal organizer of XPC positioning in higher eukaryotic chromatin

Naegeli, H

Fei, J

Kaczmarek, N

Luch, A

Glas, A

Carell, T

ZORA

Regulation of nucleotide excision repair by UV-DDB: prioritization of damage recognition to internucleosomal DNA

Jia Fei

Nina Kaczmarek

Andreas Luch

Andreas Glas

Thomas Carell

Hanspeter Naegeli

Crossref

PLoS Biology

Directory of Open Access Journals

Regulation of nucleotide excision repair by UV-DDB: prioritization of damage recognition to internucleosomal DNA.

Open Access LMU

A 127 kDa component of a UV-damaged DNA-binding complex, which is defective in some xeroderma pigmentosum group E patients, is homologous to a slime mold protein.

A DNA binding protein from human placenta specific for ultraviolet damaged DNA.

A dynamic ubiquitin equilibrium couples proteasomal activity to chromatin remodeling.

A newly identified patient with clinical xeroderma pigmentosum phenotype has a non-sense mutation in the DDB2 gene and incomplete repair in (6-4) photoproducts.

A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein.

ATP-dependent chromatin remodeling facilitates nucleotide excision repair of UV-induced DNA lesions in synthetic dinucleosomes.

Cellular concentrations of DDB2 regulate dynamic binding of DDB1 at UV-induced DNA damage.

Characterization of DNA recognition by the human UV-damaged DNAbinding protein.

Comparative analysis of binding of human damaged DNA-binding protein (XPE) and Escherichia coli damage recognition protein (UvrA) to the major ultraviolet photoproducts: T[c,s]T, T[t,s]T, T[6-4]T, and T[Dewar]T.

Contrasting structural impacts induced by cissyn cyclobutane dimer and (6-4) adduct in DNA duplex decamers: implication in mutagenesis and repair activity.

Crystal structure of the T(6-4)C lesion in complex with a (6-4) DNA photolyase and repair of UVinduced (6-4) and Dewar photolesions.

CUL4A abrogation augments DNA damage response and protection against skin carcinogenesis.

Cullin 4A associates with the UVdamaged DNA-binding protein DDB.

Cullin 4A-mediated proteolysis of DDB2 protein at DNA damage sites regulates in vivo lesion recognition by XPC.

Damaged DNA-binding protein DDB stimulates the excision of cyclobutane pyrimidine dimers in vitro in concert with XPA and replication protein A.

DDB1-DDB2 (xeroderma pigmentosum group E) protein complex recognizes a cyclobutane pyrimidine dimer, mismatches, apurinic/apyrimidinic sites, and compound lesions in DNA.

DDB2 complex-mediated ubiquitylation around DNA damage is oppositely regulated by XPC and Ku and contributes to the recruitment of XPA.

Distribution of ultravioletinduced DNA repair synthesis in nuclease sensitive and resistant regions of human chromatin.

DNA damage binding protein component DDB1 participates in nucleotide excision repair through DDB2 DNA-binding and cullin 4A ubiquitin ligase activity.

DNA damage, aging, and cancer.

DNA repair and mutagenesis. Washington DC:

DNA repair factor XPC is modified by SUMO-1 and ubiquitin following UV irradiation.

Dynamic in vivo interaction of DDB2 E3 ubiquitin ligase with UV-damaged DNA is independent of damage-recognition protein XPC.

Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair.

Extraction, purification and analysis of histones.

Heterochromatin revisited.

Histone H1 subtypes differentially modulate chromatin condensation without preventing ATP-dependent remodeling by SWI/SNF or NURF.

Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage.

Impaired regulation of tumor suppressor p53 caused by mutations in the xeroderma pigmentosum DDB2 gene: mutual regulatory interactions between p48(DDB2) and p53.

In vivo destabilization and functional defects of the xeroderma pigmentosum C protein caused by a pathogenic missense mutation.

In vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product.

Mammalian DNA nucleotide excision repair reconstituted with purified protein components.

Nonrandom induction of pyrimidine-pyrimidone (6-4) photoproducts in ultraviolet-irradiated human chromatin.

Nucleosomal structure of undamaged DNA regions suppresses the non-specific DNA binding of the XPC complex.

Nucleotide excision repair of DNA with recombinant human proteins: definition of the minimal set of factors, active forms of TFIIH, and modulation by CAK.

Recognition of DNA damage by the Rad4 nucleotide excision repair protein.

Reconstitution of human DNA repair excision nuclease in a highly defined system.

Regulation of damage recognition in mammalian global genomic nucleotide excision repair.

Sancar A

Sequential assembly of the nucleotide excision repair factors in vivo.

Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation.

Solution-state structure of a DNA dodecamer duplex containing a Cis-syn thymine cyclobutane dimer, the major UV photoproduct of DNA.

Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sites.

Structural basis of UV DNA-damage recognition by the DDB1–DDB2 complex.

The annealing helicase HARP protects stalled replication forks.

The carboxy-terminal domain of the XPC protein plays a crucial role in nucleotide excision repair through interactions with transcription factor IIH.

The DDB1-CUL4A-DDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites.

The nucleosome: from genomic organization to genomic regulation.

The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage.

The UVdamaged DNA binding protein mediates efficient targeting of the nucleotide excision repair complex to UV-induced photolesions.

The xeroderma pigmentosum group E gene product DDB2 is a specific target of cullin 4A in mammalian cells.

Translocation of a UV-damaged DNA binding protein into a tight association with chromatin after treatment of mammalian cells with UV light.

True XP group E patients have a defective UV-damaged DNA binding protein complex and mutations in DDB2 which reveal the functional domains of its p48 product.

UV induced (6-4) photoproducts are distributed differently than cyclobutane dimers in nucleosomes.

UV radiation-induced XPC translocation within chromatin is mediated by damaged-DNA binding protein, DDB2.

UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation.

UV-DDB: a molecular machine linking DNA repair with ubiquitination.

UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex.

Xeroderma pigmentosum complementation group E and UV-damaged DNA-binding protein.

Xeroderma pigmentosum group E cells lack a nuclear factor that binds to damaged DNA.

Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UVinduced mutagenesis.

Regulation of nucleotide excision repair by UV-DDB

file:///data/remote/core/dit/data/public_library_of_science/pdf/4cd/ZnRwOi8vZnRwLm5jYmkubmxtLm5paC5nb3YvcHViL3BtYy9vYV9wYWNrYWdlLzdlLzMxL1BNQzMyMDE5MjIudGFyLmd6.pdf

Regulation of Nucleotide Excision Repair by UV-DDB: Prioritization of Damage Recognition to Internucleosomal DNA

Abstract

Similar works

Full text

Available Versions

Public Library of Science (PLOS)

ZORA

Crossref

Directory of Open Access Journals

Public Library of Science (PLOS)

Open Access LMU