scholarly journals Nucleotide Excision Repair Eliminates Unique DNA-Protein Cross-links from Mammalian Cells

2007 ◽  
Vol 282 (31) ◽  
pp. 22592-22604 ◽  
Author(s):  
David J. Baker ◽  
Gerald Wuenschell ◽  
Liqun Xia ◽  
John Termini ◽  
Steven E. Bates ◽  
...  
Keyword(s):  
Nucleotide Excision Repair ◽  
Mammalian Cells ◽  
Excision Repair ◽  
Nucleotide Excision ◽  
Cross Links

scholarly journals Involvement of Nucleotide Excision Repair in a Recombination-Independent and Error-Prone Pathway of DNA Interstrand Cross-Link Repair

2001 ◽  
Vol 21 (3) ◽  
pp. 713-720 ◽  
Author(s):  
Xin Wang ◽  
Carolyn A. Peterson ◽  
Huyong Zheng ◽  
Rodney S. Nairn ◽  
Randy J. Legerski ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Nucleotide Excision Repair ◽  
Mammalian Cells ◽  
Cultured Cells ◽  
Excision Repair ◽  
Repair Pathway ◽  
Cross Link ◽  
Nucleotide Excision ◽  
Interstrand Cross Links ◽  
Cross Links

ABSTRACT DNA interstrand cross-links (ICLs) block the strand separation necessary for essential DNA functions such as transcription and replication and, hence, represent an important class of DNA lesion. Since both strands of the double helix are affected in cross-linked DNA, it is likely that conservative recombination using undamaged homologous regions as a donor may be required to repair ICLs in an error-free manner. However, in Escherichia coli and yeast, recombination-independent mechanisms of ICL repair have been identified in addition to recombinational repair pathways. To study the repair mechanisms of interstrand cross-links in mammalian cells, we developed an in vivo reactivation assay to examine the removal of interstrand cross-links in cultured cells. A site-specific psoralen cross-link was placed between the promoter and the coding region to inactivate the expression of green fluorescent protein or luciferase genes from reporter plasmids. By monitoring the reactivation of the reporter gene, we showed that a single defined psoralen cross-link was removed in repair-proficient cells in the absence of undamaged homologous sequences, suggesting the existence of an ICL repair pathway that is independent of homologous recombination. Mutant cell lines deficient in the nucleotide excision repair pathway were examined and found to be highly defective in the recombination-independent repair of ICLs, while mutants deficient in homologous recombination were found to be proficient. Mutation analysis of plasmids recovered from transfected cells showed frequent base substitutions at or near positions opposing a cross-linked thymidine residue. Based on these results, we suggest a distinct pathway for DNA interstrand cross-link repair involving nucleotide excision repair and a putative lesion bypass mechanism.

scholarly journals Nucleotide Excision Repair- and Polymerase η-Mediated Error-Prone Removal of Mitomycin C Interstrand Cross-Links

2003 ◽  
Vol 23 (2) ◽  
pp. 754-761 ◽  
Author(s):  
Huyong Zheng ◽  
Xin Wang ◽  
Amy J. Warren ◽  
Randy J. Legerski ◽  
Rodney S. Nairn ◽  
...  
Keyword(s):  
Mitomycin C ◽  
Nucleotide Excision Repair ◽  
Mammalian Cells ◽  
Excision Repair ◽  
Double Helix ◽  
Dna Lesions ◽  
Nucleotide Excision ◽  
Interstrand Cross Links ◽  
Cross Links

ABSTRACT Interstrand cross-links (ICLs) make up a unique class of DNA lesions in which both strands of the double helix are covalently joined, precluding strand opening during replication and transcription. The repair of DNA ICLs has become a focus of study since ICLs are recognized as the main cytotoxic lesion inflicted by an array of alkylating compounds used in cancer treatment. As is the case for double-strand breaks, a damage-free homologous copy is essential for the removal of ICLs in an error-free manner. However, recombination-independent mechanisms may exist to remove ICLs in an error-prone fashion. We have developed an in vivo reactivation assay that can be used to examine the removal of site-specific mitomycin C-mediated ICLs in mammalian cells. We found that the removal of the ICL from the reporter substrate could take place in the absence of undamaged homologous sequences in repair-proficient cells, suggesting a cross-link repair mechanism that is independent of homologous recombination. Systematic analysis of nucleotide excision repair mutants demonstrated the involvement of transcription-coupled nucleotide excision repair and a partial requirement for the lesion bypass DNA polymerase η encoded by the human POLH gene. From these observations, we propose the existence of a recombination-independent and mutagenic repair pathway for the removal of ICLs in mammalian cells.

scholarly journals Homologous Recombination but Not Nucleotide Excision Repair Plays a Pivotal Role in Tolerance of DNA-Protein Cross-links in Mammalian Cells

2009 ◽  
Vol 284 (40) ◽  
pp. 27065-27076 ◽  
Author(s):  
Toshiaki Nakano ◽  
Atsushi Katafuchi ◽  
Mayumi Matsubara ◽  
Hiroaki Terato ◽  
Tomohiro Tsuboi ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Nucleotide Excision Repair ◽  
Mammalian Cells ◽  
Excision Repair ◽  
Pivotal Role ◽  
Nucleotide Excision ◽  
Cross Links

scholarly journals hMutSβ Is Required for the Recognition and Uncoupling of Psoralen Interstrand Cross-Links In Vitro

2002 ◽  
Vol 22 (7) ◽  
pp. 2388-2397 ◽  
Author(s):  
Nianxiang Zhang ◽  
Xiaoyan Lu ◽  
Xiaoshan Zhang ◽  
Carolyn A. Peterson ◽  
Randy J. Legerski
Keyword(s):  
Mismatch Repair ◽  
Nucleotide Excision Repair ◽  
Mammalian Cell ◽  
Mammalian Cells ◽  
Excision Repair ◽  
Cell Extracts ◽  
Nucleotide Excision ◽  
Interstrand Cross Links ◽  
Cross Links

ABSTRACT The removal of interstrand cross-links (ICLs) from DNA in higher eucaryotes is not well understood. Here, we show that processing of psoralen ICLs in mammalian cell extracts is dependent upon the mismatch repair complex hMutSβ but is not dependent upon the hMutSα complex or hMlh1. The processing of psoralen ICLs is also dependent upon the nucleotide excision repair proteins Ercc1 and Xpf but not upon other components of the excision stage of this pathway or upon Fanconi anemia proteins. Products formed during the in vitro reaction indicated that the ICL has been removed or uncoupled from the cross-linked substrate in the mammalian cell extracts. Finally, the hMutSβ complex is shown to specifically bind to psoralen ICLs, and this binding is stimulated by the addition of PCNA. Thus, a novel pathway for processing ICLs has been identified in mammalian cells which involves components of the mismatch repair and nucleotide excision repair pathways.

Role of extracellular signal-regulated kinase (ERK) signaling in nucleotide excision repair and genotoxicity in response to As(III) and Pb(II)

2008 ◽  
Vol 80 (12) ◽  
pp. 2735-2750
Author(s):  
Ju-Pi Li ◽  
Chun-Yu Wang ◽  
Yen-An Tang ◽  
Yun-Wei Lin ◽  
Jia-Ling Yang
Keyword(s):  
Signaling Pathways ◽  
Nucleotide Excision Repair ◽  
Mammalian Cells ◽  
Excision Repair ◽  
Erk Signaling ◽  
Erk Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Nucleotide Excision

Arsenic and lead can induce genetic injuries and epigenetic signaling pathways in cultured mammalian cells. To test whether signaling pathways affect the extent of genetic injuries, we explored the impacts of extracellular signal-regulated kinase 1 and 2 (ERK) on nucleotide excision repair (NER), cytotoxicity, and genotoxicity following sodium arsenite [As(III)] and lead acetate [Pb(II)]. Sustained ERK activation was observed in human cells exposed to As(III) and Pb(II). As(III) inhibited the cellular NER synthesis capability; conversely, Pb(II) stimulated it. ERK activation contributed to the As(III)-induced NER inhibition and micronucleus formation. In contrast, this signal was required for inducing cellular NER activity and preventing mutagenesis following Pb(II). ERK activation by Pb(II) was dependent on protein kinase C (PKCα) that also exhibited anti-mutagenicity. Enforced expression of ERK signaling markedly elevated the cellular NER activity, which was suppressed by As(III). Nonetheless, ERK activation could counteract the cytotoxicity caused by these two metals. Together, the results indicate that pro-survival ERK signaling exhibits dual and opposing impacts on NER process following As(III) and Pb(II) exposures. The findings also suggest that ERK is an important epigenetic signaling in the determination of metal genotoxicity.

GENES CONTROLLING NUCLEOTIDE EXCISION REPAIR IN MAMMALIAN CELLS

1992 ◽  
pp. 235-238
Author(s):  
G. Weeda ◽  
C. Troelstra ◽  
W. Vermeulen ◽  
D. Bootsma ◽  
J.H.J. Hoeijmakers ◽  
...  
Keyword(s):  
Nucleotide Excision Repair ◽  
Mammalian Cells ◽  
Excision Repair ◽  
Nucleotide Excision

Proteins that participate in nucleotide excision repair of DNA in mammalian cells

1995 ◽  
Vol 347 (1319) ◽  
pp. 69-74 ◽  
Keyword(s):  
Nucleotide Excision Repair ◽  
Mammalian Cells ◽  
Excision Repair ◽  
Binding Activity ◽  
Main Process ◽  
Base Pairs ◽  
Inherited Disorders ◽  
Dna Binding Activity ◽  
Nucleotide Excision ◽  
Repair Defect

The most versatile strategy for repair of damage to DNA, and the main process for repair of uv-induced damage, is nucleotide excision repair. In mammalian cells, the complete mechanism involves more than 20 polypeptides, and defects in many of these are associated with various forms of inherited disorders in humans. The syndrome xeroderma pigmentosum (XP) is associated with mutagen hypersensitivity and increased cancer frequency, and studies of the nucleotide excision repair defect in this disease have been particularly informative. Many of the XP proteins are now being characterized. XPA binds to DNA, with a preference for damaged base pairs. XPC activity is part of a protein complex with single-stranded DNA binding activity. The XPG protein is a nuclease.

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