Activation of Human MutS Homologs by 8-Oxo-guanine DNA Damage

Mazurek, Anthony; Berardini, Mark; Fishel, Richard

doi:10.1074/jbc.m111269200

Cited by 154 publications

(120 citation statements)

References 50 publications

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“…Box B of the high mobility group box protein 1 (HMGB1) whose k on is close to the diffusion limit (Ϸ10 9 M Ϫ1 s Ϫ1 ) (56) selectively binds to a 1,2-d(GpG) intrastrand cross-link in the presence of human replication protein A (57), a DNA damage recognition protein in the nucleotide excision repair pathway that associates with this lesion at a rate that is about 2 orders of magnitude lower (58). In the present study our SPR assay demonstrated a k on of 3.1 ϫ 10 4 M Ϫ1 s Ϫ1 for MutS binding to the 1,2-d(GpG) intrastrand cross-link in agreement with values published for MutS and eukaryotic MutS␣ interacting with various DNA substrates (50,59,60). Thus the kinetic data obtained with MutS reveal a significantly slower rate of association as compared with box B of HMGB1 and replication protein A, and so suggest that these proteins occupy the major cisplatin intrastrand cross-link before the MMR system can trigger downstream events.…”

Section: Discussionsupporting

confidence: 90%

Binding Discrimination of MutS to a Set of Lesions and Compound Lesions (Base Damage and Mismatch) Reveals Its Potential Role as a Cisplatin-damaged DNA Sensing Protein

Fourrier

Brooks²,

Malinge³

2003

Journal of Biological Chemistry

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The DNA mismatch repair (MMR) system plays a critical role in sensitizing both prokaryotic and eukaryotic cells to the clinically potent anticancer drug cisplatin. It is thought to mediate cytotoxicity through recognition of cisplatin DNA lesions. This drug generates a range of lesions that may also give rise to compound lesions resulting from the misincorporation of a base during translesion synthesis. Using gel mobility shift competition assays and surface plasmon resonance, we have analyzed the interaction of Escherichia coli MutS protein with site-specifically modified DNA oligonucleotides containing each of the four cisplatin cross-links or a set of compound lesions. The major 1,2-d(GpG) cisplatin intrastrand cross-link was recognized with only a 1.5-fold specificity, whereas a 47-fold specificity was found with a natural G/T containing DNA substrate. The rate of association, k on, for binding to the 1,2-d(GpG) adduct was 3.1 ؋ 10 4 M ؊1 s ؊1 and the specificity of binding was essentially dependent on k off . DNA duplexes containing a single 1,2-d(ApG), 1,3-d(GpCpG) adduct, and an interstrand cross-link of cisplatin were not preferentially recognized. Among 12 DNA substrates, each containing a different cisplatin compound lesion derived from replicative misincorporation of one base opposite either of the 1,2-intrastrand adducts, 10 were specifically recognized including those that are more likely formed in vivo based on cisplatin mutation spectra. Moreover, among these lesions, two compound lesions formed when an adenine was misincorporated opposite a 1,2-d(GpG) adduct were not substrates for the MutYdependent mismatch repair pathway. The ability of MutS to sense differentially various platinated DNA substrates suggests that cisplatin compound lesions formed during misincorporation of a base opposite either adducted base of both 1,2-intrastrand cross-links are more plausible critical lesions for MMR-mediated cisplatin cytotoxicity.cis-Diamminedichloroplatinum(II) (cisplatin) 1 is among the most widely used anticancer chemotherapeutic agents in the treatment of many human tumors, particularly testicular and ovarian tumors (1). In the reaction between DNA and cisplatin, different types of bifunctional adducts are formed that are thought to be the key toxic lesions (2-4). Although these adducts are responsible for a variety of cellular responses including replication and/or transcription inhibition, there is not yet a clear understanding of the molecular mechanisms linking the formation of adducts and cisplatin-induced apoptosis (5, 6). Cisplatin reacts preferentially with the N-7 atoms of purine residues in DNA. The major adducts (90%) are 1,2-intrastrand cross-links at d(GpG) and d(ApG) sites and the minor adducts correspond to 1,3-intrastrand cross-links at d(GpNpG) (N being a nucleotide residue) and interstrand cross-links formed at d(GpC/GpC) sites (7-10). Once formed, cisplatin lesions such as the major 1,2-intrastrand cross-links can undergo replication bypass in cells treated with cisplatin (11,12). Be...

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Section: Discussionsupporting

confidence: 90%

Binding Discrimination of MutS to a Set of Lesions and Compound Lesions (Base Damage and Mismatch) Reveals Its Potential Role as a Cisplatin-damaged DNA Sensing Protein

Fourrier

Brooks²,

Malinge³

2003

Journal of Biological Chemistry

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“…Finally, oxidative damage of DNA has been correlated with the ageing process. MutSα can target 8-oxo-guanine mispairs for repair (Mazurek et al, 2002;Ni et al, 1999), and treatment of HEL cells with H 2 O 2 is associated with a reduction in MMR and with decreased levels of some MMR proteins (see, e.g. Chang et al, 2002).…”

Section: Mmr and Ageingmentioning

confidence: 99%

DNA mismatch repair: Molecular mechanism, cancer, and ageing

Hsieh

Yamane

2008

Mechanisms of Ageing and Development

397

359

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DNA mismatch repair (MMR) proteins are ubiquitous players in a diverse array of important cellular functions. In its role in post-replication repair, MMR safeguards the genome correcting base mispairs arising as a result of replication errors. Loss of MMR results in greatly increased rates of spontaneous mutation in organisms ranging from bacteria to humans. Mutations in MMR genes cause hereditary nonpolyposis colorectal cancer, and loss of MMR is associated with a significant fraction of sporadic cancers. Given its prominence in mutation avoidance and its ability to target a range of DNA lesions, MMR has been under investigation in studies of ageing mechanisms. This review summarizes what is known about the molecular details of the MMR pathway and the role of MMR proteins in cancer susceptibility and ageing.

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“…In addition to correcting single base replication errors involving undamaged bases, several studies have shown that Msh6 (but not Msh3) also participates in correcting mismatches resulting from replication of 8-oxo-G, a common lesion generated by oxidative stress [33][34][35][36][37][38]. A signature of oxidative stress-induced substitutions is a G-C to T-A transversion, which results when dAMP is incorporated opposite 8-oxo-G in its syn conformation in the template strand [39].…”

Section: The Function Of Glu339 In Yeast Msh6mentioning

confidence: 99%

Specialized mismatch repair function of Glu339 in the Phe-X-Glu motif of yeast Msh6

et al. 2007

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The major eukaryotic mismatch repair (MMR) pathway requires Msh2-Msh6, which, like E. coli MutS, binds to and participates in repair of the two most common replication errors, single base-base and single base insertion-deletion mismatches. For both types of mismatches, the side chain of E. coli Glu38 in a conserved Phe-X-Glu motif interacts with a mismatched base. The Oε of Glu38 forms a hydrogen bond with either the N7 of purines or the N3 of pyrimidines. We show here that changing E. coli Glu38 to alanine results in nearly complete loss of repair of both single base-base and single base deletion mismatches. In contrast, a yeast strain with alanine replacing homologous Glu339 in Msh6 has nearly normal repair for insertion-deletion and most base-base mismatches, but is defective in repairing base-base mismatches characteristic of oxidative stress, e.g., 8-oxo-G•A mismatches. The results suggest that bacterial MutS and yeast Msh2-Msh6 differ in how they recognize and/or process replication errors involving undamaged bases, and that Glu339 in Msh6 may have a specialized role in repairing mismatches containing oxidized bases.

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Activation of Human MutS Homologs by 8-Oxo-guanine DNA Damage

Cited by 154 publications

References 50 publications

Binding Discrimination of MutS to a Set of Lesions and Compound Lesions (Base Damage and Mismatch) Reveals Its Potential Role as a Cisplatin-damaged DNA Sensing Protein

Binding Discrimination of MutS to a Set of Lesions and Compound Lesions (Base Damage and Mismatch) Reveals Its Potential Role as a Cisplatin-damaged DNA Sensing Protein

DNA mismatch repair: Molecular mechanism, cancer, and ageing

Specialized mismatch repair function of Glu339 in the Phe-X-Glu motif of yeast Msh6

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