Molecular Basis of Transcriptional Mutagenesis at 8-Oxoguanine

Damsma, Gerke E.; Cramer, Patrick

doi:10.1074/jbc.m109.022764

Cited by 65 publications

(61 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Lesion bypass by RNAPII has been reported to occur for particular types of DNA damage such as thymine glycol, 8-oxoguanine, and O 6 -methylguanine and may lead to transcriptional mutagenesis (Doetsch 2002;Charlet-Berguerand et al 2006;Dimitri et al 2008;Damsma and Cramer 2009). Bypass of bulky helixdistorting DNA adducts and UV photolesions has also been reported to occur in certain circumstances.…”

Section: Transcriptional Arrest and Its Coupling To Dna Damage Responmentioning

confidence: 99%

Mammalian Transcription-Coupled Excision Repair

Vermeulen¹,

Fousteri

2013

Cold Spring Harbor Perspectives in Biology

157

118

View full text Add to dashboard Cite

Transcriptional arrest caused by DNA damage is detrimental for cells and organisms as it impinges on gene expression and thereby on cell growth and survival. To alleviate transcriptional arrest, cells trigger a transcription-dependent genome surveillance pathway, termed transcription-coupled nucleotide excision repair (TC-NER) that ensures rapid removal of such transcription-impeding DNA lesions and prevents persistent stalling of transcription. Defective TC-NER is causatively linked to Cockayne syndrome, a rare severe genetic disorder with multisystem abnormalities that results in patients' death in early adulthood. Here we review recent data on how damage-arrested transcription is actively coupled to TC-NER in mammals and discuss new emerging models concerning the role of TC-NER-specific factors in this process.

show abstract

Section: Transcriptional Arrest and Its Coupling To Dna Damage Responmentioning

confidence: 99%

Mammalian Transcription-Coupled Excision Repair

Vermeulen¹,

Fousteri

2013

Cold Spring Harbor Perspectives in Biology

157

118

View full text Add to dashboard Cite

show abstract

“…4,9,10 8-Oxo-7,8-dihydroguanine (8-oxoG) is the most abundant ROS-related product of DNA oxidation and has been implicated in mutagenesis. [11][12][13] The mammalian homolog 8-oxoguanine DNA glycosylase (OGG1) is enzyme specific for incising 8-oxoG to avoid the transversion of GC ? TA, or DNA damage-induced apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Combined Exercise and Insulin-Like Growth Factor-1 Supplementation Induces Neurogenesis in Old Rats, but Do Not Attenuate Age-Associated DNA Damage

Koltai

Zhao

Lacza

et al. 2011

Rejuvenation Research

View full text Add to dashboard Cite

We have investigated the effects of 2 weeks of insulin-like growth factor-1 (IGF-1) supplementation (5 mg/kg per day) and 6 weeks of exercise training (60% of the maximal oxygen consumption [VO 2 max]) on neurogenesis, DNA damage/repair, and sirtuin content in the hippocampus of young (3 months old) and old (26 months old) rats. Exercise improved the spatial memory of the old group, but IGF-1 supplementation eliminated this effect. An age-associated decrease in neurogenesis was attenuated by exercise and IGF-1 treatment. Aging increased the levels of 8-oxo-7,8-dihydroguanine (8-oxoG) and the protein Ku70, indicating the role of DNA damage in age-related neuropathology. Acetylation of 8-oxoguanine DNA glycosylase (OGG1) was detected in vivo, and this decreased with aging. However, in young animals, exercise and IGF-1 treatment increased acetylated (ac) OGG1 levels. Sirtuin 1 (SIRT1) and SIRT3, as DNA damage-associated lysine deacetylases, were measured, and SIRT1 decreased with aging, resulting in a large increase in acetylated lysine residues in the hippocampus. On the other hand, SIRT3 increased with aging. Exercise-induced neurogenesis might not be a causative factor of increased spatial memory, because IGF-1 plus exercise can induce neurogenesis in the hippocampus of older rats. Data revealed that the age-associated increase in 8-oxoG levels is due to decreased acetylation of OGG1. Age-associated decreases in SIRT1 and the associated increase in lysine acetylation, in the hippocampus, could have significant impact on function and thus, could suggest a therapeutic target.

show abstract

“…In contrast, prolonged transcriptional arrest by some bulky DNA lesions triggers either ubiquitination and degradation of pol II, or transcription-coupled nucleotide excision repair, a special DNA repair pathway that preferentially repairs DNA lesions in the transcribed strand (17,18). Structural, genetic, and biochemical studies have greatly advanced our understanding of how pol II copes with different kinds of covalent DNA lesions caused by oxidation (19,20), alkylation (21)(22)(23)(24), and photocyclo-addition (10). Less well understood are the interactions of the pol II machinery when confronted with a steric blockade by small molecules bound noncovalently in the minor groove of DNA (25)(26)(27).…”

mentioning

confidence: 99%

RNA polymerase II senses obstruction in the DNA minor groove via a conserved sensor motif

Xu¹,

Wang²,

Gotte³

et al. 2016

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

View full text Add to dashboard Cite

RNA polymerase II (pol II) encounters numerous barriers during transcription elongation, including DNA strand breaks, DNA lesions, and nucleosomes. Pyrrole-imidazole (Py-Im) polyamides bind to the minor groove of DNA with programmable sequence specificity and high affinity. Previous studies suggest that Py-Im polyamides can prevent transcription factor binding, as well as interfere with pol II transcription elongation. However, the mechanism of pol II inhibition by Py-Im polyamides is unclear. Here we investigate the mechanism of how these minor-groove binders affect pol II transcription elongation. In the presence of site-specifically bound Py-Im polyamides, we find that the pol II elongation complex becomes arrested immediately upstream of the targeted DNA sequence, and is not rescued by transcription factor IIS, which is in contrast to pol II blockage by a nucleosome barrier. Further analysis reveals that two conserved pol II residues in the Switch 1 region contribute to pol II stalling. Our study suggests this motif in pol II can sense the structural changes of the DNA minor groove and can be considered a "minor groove sensor." Prolonged interference of transcription elongation by sequence-specific minor groove binders may present opportunities to target transcription addiction for cancer therapy.Py-Im polyamide | transcription inhibition | minor groove | DNA I n eukaryotes, precursor mRNA synthesis is catalyzed by the RNA polymerase II holoenzyme (pol II), which frequently pauses during transcription elongation (1-3). In addition to regulatory factors that control pol II processivity, various obstacles encountered by pol II can also lead to stalling, and even backtracking, on the DNA template (4). Factors that affect pol II transcription elongation dynamics include intrinsic DNA sequences or structures (5, 6), endogenous epigenetic DNA modifications (7), embedded ribonucleotides (8), DNA lesions (9, 10), small-molecule DNA-binders (11, 12), DNA-binding proteins including nucleosomes (13), and even pol II itself (14, 15). Transient transcriptional pausing or short-lived transcriptional blockage can be rescued by the recruitment of transcription factor IIS (TFIIS) (16, 17), a transcription factor that facilitates the cleavage of backtracked transcript. In contrast, prolonged transcriptional arrest by some bulky DNA lesions triggers either ubiquitination and degradation of pol II, or transcription-coupled nucleotide excision repair, a special DNA repair pathway that preferentially repairs DNA lesions in the transcribed strand (17, 18). Structural, genetic, and biochemical studies have greatly advanced our understanding of how pol II copes with different kinds of covalent DNA lesions caused by oxidation (19, 20), alkylation (21-24), and photocyclo-addition (10). Less well understood are the interactions of the pol II machinery when confronted with a steric blockade by small molecules bound noncovalently in the minor groove of DNA (25-27).Pyrrole-imidazole (Py-Im) polyamides are a class of small molecules that c...

show abstract

Molecular Basis of Transcriptional Mutagenesis at 8-Oxoguanine

Cited by 65 publications

References 35 publications

Mammalian Transcription-Coupled Excision Repair

Mammalian Transcription-Coupled Excision Repair

Combined Exercise and Insulin-Like Growth Factor-1 Supplementation Induces Neurogenesis in Old Rats, but Do Not Attenuate Age-Associated DNA Damage

RNA polymerase II senses obstruction in the DNA minor groove via a conserved sensor motif

Contact Info

Product

Resources

About