Enhanced repair of DNA interstrand crosslinks in S phase

Mladenova, Veronika; Russev, George

doi:10.1016/j.febslet.2006.02.009

Cited by 8 publications

(6 citation statements)

References 22 publications

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“…The examination of nucleotide excision repair (NER) and transcription coupled repair in synchronized and UV irradiated Chinese hamster ovary (CHO) cells in G1 and G2 phases identified no major differences [ 32 ]. Recent studies on synchronized Hela cells in G1 and S phases found that the S phase cells repaired DNA interstrand crosslinks more efficiently than G1-phase cells [ 33 ]. Our data has shown that there is a marked difference in BER activities in irradiated G1 and G2 enriched cells.…”

Section: Discussionmentioning

confidence: 99%

Base excision repair of ionizing radiation-induced DNA damage in G1 and G2 cell cycle phases

Chaudhry

2007

Cancer Cell Int

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BackgroundMajor genomic surveillance mechanisms regulated in response to DNA damage exist at the G1/S and G2/M checkpoints. It is presumed that these delays provide time for the repair of damaged DNA. Cells have developed multiple DNA repair pathways to protect themselves from different types of DNA damage. Oxidative DNA damage is processed by the base excision repair (BER) pathway. Little is known about the BER of ionizing radiation-induced DNA damage and putative heterogeneity of BER in the cell cycle context. We measured the activities of three BER enzymes throughout the cell cycle to investigate the cell cycle-specific repair of ionizing radiation-induced DNA damage. We further examined BER activities in G2 arrested human cells after exposure to ionizing radiation.ResultsUsing an in vitro incision assay involving radiolabeled oligonucleotides with specific DNA lesions, we examined the activities of several BER enzymes in the whole cell extracts prepared from synchronized human HeLa cells irradiated in G1 and G2 phase of the cell cycle. The activities of human endonuclease III (hNTH1), a glycosylase/lyase that removes several damaged bases from DNA including dihydrouracil (DHU), 8-oxoguanine-DNA glycosylase (hOGG1) that recognizes 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxoG) lesion and apurinic/apyrimidinic endonuclease (hAPE1) that acts on abasic sites including synthetic analog furan were examined.ConclusionOverall the repair activities of hNTH1 and hAPE1 were higher in the G1 compared to G2 phase of the cell cycle. The percent cleavages of oligonucleotide substrate with furan were greater than substrate with DHU in both G1 and G2 phases. The irradiation of cells enhanced the cleavage of substrates with furan and DHU only in G1 phase. The activity of hOGG1 was much lower and did not vary within the cell cycle. These results demonstrate the cell cycle phase dependence on the BER of ionizing radiation-induced DNA damage. Interestingly no evidence of enhanced BER activities was found in irradiated cells arrested in G2 phase.

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Section: Discussionmentioning

confidence: 99%

Base excision repair of ionizing radiation-induced DNA damage in G1 and G2 cell cycle phases

Chaudhry

2007

Cancer Cell Int

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“…The ICL repair events are shown to be both replication-dependent [49] and replication-independent [50]. The replication-dependent ICL repair occurs in S or G2 phase of the cell cycle [51, 52]. ICL repair is initiated by DNA replication fork collapse which activates signaling pathways for cell cycle arrest, to repair the DNA lesion [53].…”

Section: Interstrand Crosslinks (Icls)mentioning

confidence: 99%

Evidence for base excision repair processing of DNA interstrand crosslinks

Kothandapani

Patrick

2013

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Many bifunctional alkylating agents and anticancer drugs exert their cytotoxicity by producing cross links between the two complementary strands of DNA, termed interstrand crosslinks (ICLs). This blocks the strand separating processes during DNA replication and transcription, which can lead to cell cycle arrest and apoptosis. Cells use multiple DNA repair systems to eliminate the ICLs. Concerted action of repair proteins involved in Nucleotide Excision Repair and Homologous Recombination pathways are suggested to play a key role in the ICL repair. However, recent studies indicate a possible role for Base Excision Repair (BER) in mediating the cytotoxicity of ICL inducing agents in mammalian cells. Elucidating the mechanism of BER mediated modulation of ICL repair would help in understanding the recognition and removal of ICLs and aid in the development of potential therapeutic agents. In this review, the influence of BER proteins on ICL DNA repair and the possible mechanisms of action are discussed.

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“…Genetic data implicate the involvement of the Ercc1-Xpf endonuclease complex of the nucleotide excision repair pathway and proteins required for homologous recombination (HR) mediated repair of double-strand breaks (DSBs) (Dronkert and Kanaar, 2001;Sancar et al, 2004). Most current models suggest that the repair of ICLs induced by photoactivated psoralens in mammalian cells occurs primarily during S-phase and that DSBs are intermediates of ICL repair (Rothfuss and Grompe, 2004;Niedernhofer et al, 2005;Mladenova and Russev, 2006). ICL formation does not trigger G1/S and G2/M checkpoints and regardless of the phase of the cell cycle during which the damage is induced, cells are arrested in S-phase (Akkari et al, 2000).…”

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confidence: 98%

Activation of the S phase DNA damage checkpoint by mitomycin C

Mladenov

Tsaneva

Anachkova

2006

Journal Cellular Physiology

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We have studied the rate of DNA synthesis, cell cycle distribution, formation of gamma-H2AX, and Rad51 nuclear foci and association of Rad51 with the nuclear matrix after treatment of HeLa cells with the interstrand crosslinking agent mitomycin C (MMC) in the presence of the kinase inhibitors caffeine and wortmannin. The results showed that MMC treatment arrested the cells in S-phase and induced the appearance of gamma-H2AX and Rad51 nuclear foci, accompanied with a sequestering of Rad51 to the nuclear matrix. These effects were abrogated by caffeine, which inhibits the Ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) kinases. However, wortmannin at a concentration that inhibits ATM, but not ATR did not affect cell cycle progression, damage-induced phosphorylation of H2AX and Rad51 foci formation, and association with the nuclear matrix, suggesting that the S-phase arrest induced by MMC is ATR-dependent. These findings were confirmed by experiments with ATR-deficient and AT cells. They indicate that the DNA damage ATR-dependent S-phase checkpoint pathway may regulate the spatiotemporal organization of the process of repair of interstrand crosslinks.

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Enhanced repair of DNA interstrand crosslinks in S phase

Cited by 8 publications

References 22 publications

Base excision repair of ionizing radiation-induced DNA damage in G1 and G2 cell cycle phases

Base excision repair of ionizing radiation-induced DNA damage in G1 and G2 cell cycle phases

Evidence for base excision repair processing of DNA interstrand crosslinks

Activation of the S phase DNA damage checkpoint by mitomycin C

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