Repair by human cell extracts of single (6-4) and cyclobutane thymine-thymine photoproducts in DNA.

Szymkowski, David E.; Lawrence, Christopher W.; Wood, Richard D.

doi:10.1073/pnas.90.21.9823

Cited by 82 publications

(68 citation statements)

References 43 publications

(52 reference statements)

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“…Thymine cyclobutane dimer (TϽϾT), compared to T T, is a notoriously poor substrate for excision repair (42,58,60). Unlike T T, the cyclobutane dimer is also a poor replicational block (7,57,64), allowing translesion replication with occasional misincorporation (62).…”

Section: Discussionmentioning

confidence: 99%

Recognition and Repair of Compound DNA Lesions (Base Damage and Mismatch) by Human Mismatch Repair and Excision Repair Systems

Tursun

Duckett

et al. 1997

Molecular and Cellular Biology

185

133

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Nucleotide excision repair and the long-patch mismatch repair systems correct abnormal DNA structures arising from DNA damage and replication errors, respectively. DNA synthesis past a damaged base (translesion replication) often causes misincorporation at the lesion site. In addition, mismatches are hot spots for DNA damage because of increased susceptibility of unpaired bases to chemical modification. We call such a DNA lesion, that is, a base damage superimposed on a mismatch, a compound lesion. To learn about the processing of compound lesions by human cells, synthetic compound lesions containing UV photoproducts or cisplatin 1,2-d(GpG) intrastrand cross-link and mismatch were tested for binding to the human mismatch recognition complex hMutS␣ and for excision by the human excision nuclease. No functional overlap between excision repair and mismatch repair was observed. The presence of a thymine dimer or a cisplatin diadduct in the context of a G-T mismatch reduced the affinity of hMutS␣ for the mismatch. In contrast, the damaged bases in these compound lesions were excised three-to fourfold faster than simple lesions by the human excision nuclease, regardless of the presence of hMutS␣ in the reaction. These results provide a new perspective on how excision repair, a cellular defense system for maintaining genomic integrity, can fix mutations under certain circumstances.Mismatches in DNA resulting from replication errors, and base damage caused by physical (UV light) and chemical (polyaromatic hydrocarbons) agents, are responsible for the majority of human cancers (18). Although certain mismatches and base lesions can be eliminated from DNA by the base excision repair pathway initiated by glycosylases with narrow substrate ranges, in human cells there exists a general mismatch repair system and a general damage repair system of wide substrate range. The mismatch repair system removes the mismatched base as a nucleotide (44), and the excision repair system excises the damaged base(s) in an oligonucleotide (52, 67).The general mismatch repair system (long-patch mismatch repair) corrects all eight single-base mismatches as well as small insertion sequence loops with comparable efficiencies (31, 44). The general nucleotide excision repair (excision repair) system (8) not only is the sole repair pathway for bulky lesions such as thymine dimers (TϽϾT) and cisplatin-guanine adducts but also repairs a wide variety of nonbulky lesions such as O 6 -methylguanine (O 6 -meG) at physiologically relevant rates (52). Thus, it appears that both repair systems recognize many dissimilar non-B DNA forms rather than a specific lesion structure.Given the wide substrate ranges of both systems, it is not unreasonable to expect overlaps between the two substrate spectra, or that one repair system may facilitate the function of the other. Indeed, it has been shown that the excision repair system recognizes mismatches and removes the mismatched base in a manner identical to the removal of damaged bases (27). Since a DNA lesion, by de...

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Section: Discussionmentioning

confidence: 99%

Recognition and Repair of Compound DNA Lesions (Base Damage and Mismatch) by Human Mismatch Repair and Excision Repair Systems

Tursun

Duckett

et al. 1997

Molecular and Cellular Biology

185

133

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“…Mammalian NER processes a wide range of chemically and structurally distinct base adducts, but some types of damage are repaired at higher rates than others (1,2,10,45,46). The biochemical mechanisms underlying this broad and extremely heterogeneous response are poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…For example, cyclobutane pyrimidine dimers are processed in vivo and in vitro at a considerably lower rate than pyrimidine(6-4) photoproducts (45,46,50). The thermodynamic properties of DNA fragments containing a cyclobutane dimer indicate that this lesion minimally affects the ability to form a duplex (51), whereas pyrimidine(6-4) photoproducts strongly favor disruption of the double helix (52).…”

Section: Discussionmentioning

confidence: 99%

Recognition of DNA Adducts by Human Nucleotide Excision Repair

Gunz

Heß

Naegeli

1996

Journal of Biological Chemistry

187

147

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The mechanism by which mammalian nucleotide excision repair (NER) detects a wide range of base lesions is poorly understood. Here, we tested the ability of human NER to recognize bulky modifications that either destabilize the DNA double helix (acetylaminofluorene (AAF) and benzo[a]pyrene diol-epoxide (BPDE) adducts, UV radiation products) or induce opposite effects by stabilizing the double helix (8-methoxypsoralen (8-MOP), anthramycin, and CC-1065 adducts). We constructed plasmid DNA carrying a defined number of each of these adducts and determined their potential to sequester NER factors contained in a human cell-free extract. For that purpose, we measured the capacity of damaged plasmids to compete with excision repair of a site-directed NER substrate. This novel approach showed differences of more than 3 orders of magnitude in the efficiency by which helix-destabilizing and helixstabilizing adducts sequester NER factors. For example, AAF modifications were able to compete with the NER substrate ϳ1740 times more effectively than 8-MOP adducts. The sequestration potency decreased with the following order of adducts, AAF > UV BPDE > 8-MOP > anthramycin, CC-1065. A strong preference for helix-destabilizing lesions was confirmed by monitoring the formation of NER patches at site-specific adducts with either AAF or CC-1065. This comparison based on factor sequestration and repair synthesis indicates that human NER is primarily targeted to sites at which the secondary structure of DNA is destabilized. Thus, an early step of DNA damage recognition involves thermodynamic probing of the duplex. Nucleotide excision repair (NER)1 is an essential pathway for removing bulky base modifications from DNA. This repair mechanism involves endonucleolytic cleavage at two phosphodiester bonds, one 3Ј and the other 5Ј of the site of damage, followed by excision of DNA damage as the component of a single-stranded fragment (1-5). The excised oligonucleotide is replaced by DNA repair synthesis, and DNA continuity is reestablished by ligation. In mammalian cells, the major sites of incision are at the 5th phosphodiester bond 3Ј and the 24th phosphodiester bond 5Ј to the lesion (6).

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“…However, both diastereoisomers were relatively poor NER substrates compared with the 1,3-intrastrand d(GpTpG)-cisplatin crosslink, which is in a well-repaired class of lesions that include (6-4) pyrimidine photoproducts and acetylaminofluorene-G lesions (27,28). In this regard, the cyPu resemble cyclobutane pyrimidine dimers, which are also only sluggishly repaired by the NER system (27,28). Nevertheless, both diastereoisomers of cyPu residues can clearly be removed from DNA by NER.…”

Section: Oligonucleotides Formed By Dual Incision Of Dna Containing Amentioning

confidence: 99%

Removal of oxygen free-radical-induced 5′,8-purine cyclodeoxynucleosides from DNA by the nucleotide excision-repair pathway in human cells

Kuraoka

Bender

Romieu

et al. 2000

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

342

380

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Exposure of cellular DNA to reactive oxygen species generates several classes of base lesions, many of which are removed by the base excision-repair pathway. However, the lesions include purine cyclodeoxynucleoside formation by intramolecular crosslinking between the C-8 position of adenine or guanine and the 5 position of 2-deoxyribose. This distorting form of DNA damage, in which the purine is attached by two covalent bonds to the sugarphosphate backbone, occurs as distinct diastereoisomers. It was observed here that both diastereoisomers block primer extension by mammalian and microbial replicative DNA polymerases, using DNA with a site-specific purine cyclodeoxynucleoside residue as template, and consequently appear to be cytotoxic lesions. Plasmid DNA containing either the 5 R or 5 S form of 5 ,8-cyclo-2-deoxyadenosine was a substrate for the human nucleotide excision-repair enzyme complex. The R diastereoisomer was more efficiently repaired than the S isomer. No correction of the lesion by direct damage reversal or base excision repair was detected. Dual incision around the lesion depended on the core nucleotide excision-repair protein XPA. In contrast to several other types of oxidative DNA damage, purine cyclodeoxynucleosides are chemically stable and would be expected to accumulate at a slow rate over many years in the DNA of nonregenerating cells from xeroderma pigmentosum patients. High levels of this form of DNA damage might explain the progressive neurodegeneration seen in XPA individuals.endogenous DNA lesions ͉ xeroderma pigmentosum ͉ neurodegeneration

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Repair by human cell extracts of single (6-4) and cyclobutane thymine-thymine photoproducts in DNA.

Abstract: One cis-syn cyclobutane thymine dimer or one (6-4) thymine-thymine photoproduct was built into an identical sequence of a closed-circular M13 duplex DNA, and nucleotide excision repair synthesis carried out by human cell extracts in the area containing each lesion was determined.

Cited by 82 publications

References 43 publications

Recognition and Repair of Compound DNA Lesions (Base Damage and Mismatch) by Human Mismatch Repair and Excision Repair Systems

Recognition and Repair of Compound DNA Lesions (Base Damage and Mismatch) by Human Mismatch Repair and Excision Repair Systems

Recognition of DNA Adducts by Human Nucleotide Excision Repair

Removal of oxygen free-radical-induced 5′,8-purine cyclodeoxynucleosides from DNA by the nucleotide excision-repair pathway in human cells

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