Human and yeast DNA damage recognition complexes bind with high affinity DNA structures mimicking in size transcription bubble

Krasikova, Y. S.; Rechkunova, N. I.; Maltseva, Ekaterina A.; Anarbaev, Rashid O.; Pestryakov, P. E.; Sugasawa, Kaoru; Min, Jo Young; Lavrik, Olga I.

doi:10.1002/jmr.2308

Cited by 12 publications

(16 citation statements)

References 30 publications

(41 reference statements)

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“…Indeed, it seems quite remarkable that without requiring major changes to the overall evolutionarily conserved 3D shape and structure of the mammalian XPC complex, it has nevertheless adopted entirely new transcriptional coactivator functions in the context of ES cell regulatory pathways that are not relevant in yeast. The extent of structural conservation is consistent with their equivalence in repair (22). Regions displaying differences may reflect the divergence in functional capabilities that we observe in a transcriptional context (Fig.…”

Section: Discussionsupporting

confidence: 82%

“…The similarity between the dsDNA-and ssDNA-bound structures is consistent with the fact that the XPC complex is capable of binding a large suite of different DNA structures, including UVinduced thymine dimers (2), mismatch bubbles (22), ssDNAdsDNA junctions (39), apurinic/apyrimidic (AP) sites (40), and even undamaged duplex and certain single-stranded DNA substrates (33). This similarity between different DNA-bound structures is also consistent with recent work describing a kinetic but not structural means of discrimination between damaged and undamaged DNA by Rad4 (41).…”

Section: Discussionsupporting

confidence: 65%

“…The partial crystal structure of Rad4, the yeast homolog of the human XPC subunit, in complex with the Rad4-interaction domain of yeast Rad23, has provided information helpful toward an understanding of Rad4/ XPC's biochemical behavior and of certain phenotypic outcomes (18,21). However, given XPC's low sequence homology with the yeast homolog Rad4 (21,22), the absence of key domains in the available crystal structure, and the divergence of requirements for transcriptional vs. repair activities (4,15,18,23), structural information of the complete, three-subunit, native human XPC complex is much needed for an understanding of the functional versatility of the XPC complex. At present, no information has been reported on the overall architecture of the XPC holocomplex, the possible large-scale conformational rearrangements in XPC upon DNA-binding, or the extent of structural conservation of the human XPC complex with homolog complexes.…”

Section: Significancementioning

confidence: 99%

“…S4 A and B). The 48-bp DNA bubble mismatch duplex was chosen from a validated EMSA probe (22) that demonstrated one of the strongest affinities for the XPC complex. Comparison of the reconstructions obtained from the apo vs. DNA-bound samples indicates that the addition of DNA primarily affected the density region immediately above the "earlobe" (Fig.…”

Section: Ab Initio 3d Reconstruction Of the Human Xpc Complex By Randommentioning

confidence: 99%

“…The human XPC complex (XPC, RAD23B, CETN2) and the yeast homolog Rad4 complex (Rad4, Rad23, Rad33; ref. 34) appear to function equivalently in nucleotide excision repair, given their similar binding properties to damaged DNA (22). These two complexes are also thought to be structurally similar based on strong sequence homology between human RAD23B and yeast Rad23 (6) and between human CETN2 and the purported yeast CETN2 homolog Rad33 (Fig.…”

Section: Ab Initio 3d Reconstruction Of the Human Xpc Complex By Randommentioning

confidence: 99%

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Architecture of the human XPC DNA repair and stem cell coactivator complex

Zhang

Grob

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The Xeroderma pigmentosum complementation group C (XPC) complex is a versatile factor involved in both nucleotide excision repair and transcriptional coactivation as a critical component of the NANOG, OCT4, and SOX2 pluripotency gene regulatory network. Here we present the structure of the human holo-XPC complex determined by single-particle electron microscopy to reveal a flexible, ear-shaped structure that undergoes localized loss of order upon DNA binding. We also determined the structure of the complete yeast homolog Rad4 holo-complex to find a similar overall architecture to the human complex, consistent with their shared DNA repair functions. Localized differences between these structures reflect an intriguing phylogenetic divergence in transcriptional capabilities that we present here. Having positioned the constituent subunits by tagging and deletion, we propose a model of key interaction interfaces that reveals the structural basis for this difference in functional conservation. Together, our findings establish a framework for understanding the structure-function relationships of the XPC complex in the interplay between transcription and DNA repair.transcription | stem cells | DNA repair | structure | biochemistry

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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 65%

Section: Significancementioning

confidence: 99%

Section: Ab Initio 3d Reconstruction Of the Human Xpc Complex By Randommentioning

confidence: 99%

Section: Ab Initio 3d Reconstruction Of the Human Xpc Complex By Randommentioning

confidence: 99%

See 3 more Smart Citations

Architecture of the human XPC DNA repair and stem cell coactivator complex

Zhang

Grob

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Nucleotide Excision Repair and Transcription‐Associated Genome Instability

et al. 2019

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Transcription is a potential threat to genome integrity, and transcription‐associated DNA damage must be repaired for proper messenger RNA (mRNA) synthesis and for cells to transmit their genome intact into progeny. For a wide range of structurally diverse DNA lesions, cells employ the highly conserved nucleotide excision repair (NER) pathway to restore their genome back to its native form. Recent evidence suggests that NER factors function, in addition to the canonical DNA repair mechanism, in processes that facilitate mRNA synthesis or shape the 3D chromatin architecture. Here, these findings are critically discussed and a working model that explains the puzzling clinical heterogeneity of NER syndromes highlighting the relevance of physiological, transcription‐associated DNA damage to mammalian development and disease is proposed.

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The role of Transcription Factor IIH complex in nucleotide excision repair

Hoag,

Duan,

Mao

2023

Environ and Mol Mutagen

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DNA damage occurs throughout life from a variety of sources, and it is imperative to repair damage in a timely manner to maintain genome stability. Thus, DNA repair mechanisms are a fundamental part of life. Nucleotide Excision Repair (NER) plays an important role in the removal of bulky DNA adducts, such as cyclobutane pyrimidine dimers (CPDs) from ultraviolet (UV) light or DNA crosslinking damage from platinum‐based chemotherapeutics, such as cisplatin. A main component for the NER pathway is transcription factor IIH (TFIIH), a multifunctional, 10‐subunit protein complex with crucial roles in both transcription and NER. In transcription, TFIIH is a component of the pre‐initiation complex (PIC) and is important for promoter opening and the phosphorylation of RNA Polymerase II (RNA Pol II). During repair, TFIIH is important for DNA unwinding, recruitment of downstream repair factors, and verification of the bulky lesion. Several different disease states can arise from mutations within subunits of the TFIIH complex. Most strikingly are Xeroderma Pigmentosum (XP), XP combined with Cockayne Syndrome (CS), and Trichothiodystrophy (TTD). Here, we summarize the recruitment and functions of TFIIH in the two NER subpathways, global genomic (GG‐NER) and transcription‐coupled NER (TC‐NER). We will also discuss how TFIIH's roles in the two subpathways lead to different genetic disorders.This article is protected by copyright. All rights reserved.

show abstract

Human and yeast DNA damage recognition complexes bind with high affinity DNA structures mimicking in size transcription bubble

Cited by 12 publications

References 30 publications

Architecture of the human XPC DNA repair and stem cell coactivator complex

Architecture of the human XPC DNA repair and stem cell coactivator complex

Nucleotide Excision Repair and Transcription‐Associated Genome Instability

The role of Transcription Factor IIH complex in nucleotide excision repair

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