S. cerevisiae has three pathways for DNA interstrand crosslink repair

Grossmann, Kenneth F.; Ward, Alex M.; Matkovic, Mara; Folias, Alexandra E.; Moses, Robb E.

doi:10.1016/s0921-8777(01)00106-9

Cited by 100 publications

(108 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although results from yeast suggest that pol η does not confer resistance to ICL by cisplatin [5], XP-V cells have been reported to be hypersensitive to and impaired in the repair of a number of DNA damaging agents, including ICL-forming agents, suggesting that TLS by pol η is important in lesion tolerance and survival following ICL in humans [17,20,32,39]. However, most prior studies of pol η and ICLs have been performed utilizing plasmid substrates, rather than analyzing genomic DNA [18][19][20].…”

Section: Discussionmentioning

confidence: 99%

“…In yeast and mammalian cells, nucleotide excision repair (NER), recombination, and translesion synthesis, as well as certain mismatch repair proteins, have been reported to participate in ICL repair [2,[5][6][7][8][9][10]. Recombinational repair is in part thought to be a response to formation of double-strand breaks (DSBs) at ICL that appear to be unique to eukaryotes and that arise either as a result of collapsed replication forks blocked at ICL, or as true repair intermediates [8,9,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…This polymerase is mutated in cells from individuals with the variant form of xeroderma pigmentosum (XP-V) who are prone to skin cancers yet are NER-proficient. While rad30-deficient yeast lacking pol η are not dramatically more sensitive to some ICL agents [5], studies in XP-V cells have suggested that pol η is important for ICL repair in humans. XP-V cells are hypersensitive to psoralen photoadducts, including ICL [17], exhibit increased mutagenesis in response to psoralen ICL associated with triplex-forming oligonucleotides [18], are moderately impaired in reactivation of psoralen crosslinked reporter plasmids [19], and are defective in recombination-independent ICL repair of mitomycin C-induced ICL in a plasmid reporter reactivation assay [20].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

DNA polymerase η reduces the γ-H2AX response to psoralen interstrand crosslinks in human cells

Mogi

Butcher

2008

Experimental Cell Research

View full text Add to dashboard Cite

DNA interstrand crosslinks are processed by multiple mechanisms whose relationships to each other are unclear. Xeroderma pigmentosum-variant (XP-V) cells lacking DNA polymerase η are sensitive to psoralen photoadducts created under conditions favoring crosslink formation, suggesting a role for translesion synthesis in crosslink repair. Because crosslinks can lead to double strand breaks, we monitored phosphorylated H2AX (γ-H2AX), which is typically generated near double-strand breaks but also in response to single-stranded DNA, following psoralen photoadduct formation in XP-V fibroblasts to assess whether polymerase η is involved in processing crosslinks. In contrast to conditions favoring monoadducts, conditions favoring psoralen crosslinks induced γ-H2AX levels in both XP-V and nucleotide excision repair-deficient XP-A cells relative to control repair-proficient cells; ectopic expression of polymerase η in XP-V cells normalized the γ-H2AX response. In response to psoralen crosslinking, γ-H2AX as well as 53BP1 formed co-incident foci that were more numerous and intense in XP-V and XP-A cells than in controls. Psoralen photoadducts induced γ-H2AX throughout the cell cycle in XP-V cells. These results indicate that polymerase η is important in responding to psoralen crosslinks, and are consistent with a model in which nucleotide excision repair and polymerase η are involved in processing crosslinks and avoiding γ-H2AX associated with double strand breaks and single-stranded DNA in human cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

DNA polymerase η reduces the γ-H2AX response to psoralen interstrand crosslinks in human cells

Mogi

Butcher

2008

Experimental Cell Research

View full text Add to dashboard Cite

show abstract

“…It was also shown in this same report that Snm1 has a separate role in G1 phase repair of ICLs that requires the nucleotide excision repair pathway, but not homologous recombination. Thus, Snm1 plays a role in both homology-dependent and homology-independent pathways of ICL repair in Saccharomyces cerevisiae (Grossmann et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Snm1B/Apollo mediates replication fork collapse and S Phase checkpoint activation in response to DNA interstrand cross-links

et al. 2008

View full text Add to dashboard Cite

The removal of DNA interstrand cross-links (ICLs) has proven to be notoriously complicated due to the involvement of multiple pathways of DNA repair, which include the Fanconi anemia/BRCA pathway, homologous recombination and components of the nucleotide excision and mismatch repair pathways. Members of the SNM1 gene family have also been shown to have a role in mediating cellular resistance to ICLs, although their precise function has remained elusive. Here, we show that knockdown of Snm1B/Apollo in human cells results in hypersensitivity to mitomycin C (MMC), but not to IR. We also show that Snm1B-deficient cells exhibit a defective S phase checkpoint in response to MMC, but not to IR, and this finding may account for the specific sensitivity to the cross-linking drug. Interestingly, although previous studies have largely implicated ATR as the major kinase activated in response to ICLs, we show that it is activation of the ATMmediated checkpoint that is defective in Snm1B-deficient cells. The requirement for Snm1B in ATM checkpoint activation specifically after ICL damage is correlated with its role in promoting double-strand break formation, and thus replication fork collapse. Consistent with this result Snm1B was found to interact directly with Mus81-Eme1, an endonuclease previously implicated in fork collapse. In addition, we also show that Snm1B interacts with the Mre11-Rad50-Nbs1 (MRN) complex and with FancD2 further substantiating its role as a checkpoint/DNA repair protein.

show abstract

“…A second round of NER action removes the remaining monoadduct. In yeast, a third poorly understood pathway involving SNM1 may also be present [8,9].…”

Section: Introductionmentioning

confidence: 99%

Double-strand breaks induce homologous recombinational repair of interstrand cross-links via cooperation of MSH2, ERCC1-XPF, REV3, and the Fanconi anemia pathway

Zhang

Liu

et al. 2007

DNA Repair

View full text Add to dashboard Cite

DNA interstrand cross-linking agents have been widely used in chemotherapeutic treatment of cancer. The majority of interstrand cross-links (ICLs) in mammalian cells are removed via a complex process that involves the formation of double strand breaks at replication forks, incision of the ICL, and subsequent error-free repair by homologous recombination. How double strand breaks effect the removal of ICLs and the downstream homologous recombination process is not clear. Here, we describe a plasmid-based recombination assay in which one copy of the CFP gene is inactivated by a site-specific psoralen ICL and can be repaired by gene conversion with a mutated homologous donor sequence. We found that the homology dependent recombination (HDR) is inhibited by the ICL. However, when we introduced a double strand break adjacent to the site of the ICL, the removal of the ICL was enhanced and the substrate was funneled into a HDR repair pathway. This process was not dependent on the nucleotide excision repair pathway, but did require the ERCC1-XPF endonuclease and REV3. In addition, both the Fanconi anemia pathway and the mismatch repair protein MSH2 were required for the recombinational repair processing of the ICL. These results suggest that the juxtaposition of an ICL and a DSB stimulates repair of ICLs through a process requiring components of mismatch repair, ERCC1-XPF, REV3, Fanconi anemia proteins, and homologous recombination repair factors.

show abstract

S. cerevisiae has three pathways for DNA interstrand crosslink repair

Cited by 100 publications

References 36 publications

DNA polymerase η reduces the γ-H2AX response to psoralen interstrand crosslinks in human cells

DNA polymerase η reduces the γ-H2AX response to psoralen interstrand crosslinks in human cells

Snm1B/Apollo mediates replication fork collapse and S Phase checkpoint activation in response to DNA interstrand cross-links

Double-strand breaks induce homologous recombinational repair of interstrand cross-links via cooperation of MSH2, ERCC1-XPF, REV3, and the Fanconi anemia pathway

Contact Info

Product

Resources

About