Repair of DNA interstrand crosslinks may take place at the nuclear matrix

Atanassov, Boyko S.; Gospodinov, Anastas; Stoimenov, Ivaylo; Mladenov, Emil; Russev, George; Tsaneva, Irina R.; Anachkova, Boyka

doi:10.1002/jcb.20518

Cited by 11 publications

(10 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been demonstrated that α IISp interacts with the nuclear matrix (Bachs et al 1990) and this observation is consistent with data demonstrating that the nuclear matrix may serve as an important locus for ICL repair (Atanassov et al 2005). …”

Section: Icl Repair In Quiescent Dnasupporting

confidence: 84%

Initiation of DNA interstrand cross‐link repair in mammalian cells

Hlavin

Smeaton

Miller

2010

Environ and Mol Mutagen

View full text Add to dashboard Cite

Interstrand cross-links (ICLs) are among the most cytotoxic DNA lesions to cells because they prevent the two DNA strands from separating, thereby precluding replication and transcription. Even though chemotherapeutic cross-linking agents are well established in clinical use, and numerous repair proteins have been implicated in the initial events of mammalian ICL repair, the precise mechanistic details of these events remain to be elucidated. This review will summarize our current understanding of how ICL repair is initiated with an emphasis on the context (replicating, transcribed or quiescent DNA) in which the ICL is recognized, and how the chemical and physical properties of ICLs influence repair. Although most studies have focused on replication-dependent repair because of the relation to highly replicative tumor cells, replicationindependent ICL repair is likely to be important in the circumvention of cross-link cytotoxicity in non-dividing, terminally differentiated cells that may be challenged with exogenous or endogenous sources of ICLs. Consequently, the ICL repair pathway that should be considered 'dominant' appears to depend on the cell type and the DNA context in which the ICL is encountered. The ability to define and inhibit distinct pathways of ICL repair in different cell cycle phases may help in developing methods that increase cytotoxicity to cancer cells while reducing side-effects in non-dividing normal cells. This may also lead to a better understanding of pathways that protect against malignancy and aging.

show abstract

Section: Icl Repair In Quiescent Dnasupporting

confidence: 84%

Initiation of DNA interstrand cross‐link repair in mammalian cells

Hlavin

Smeaton

Miller

2010

Environ and Mol Mutagen

View full text Add to dashboard Cite

show abstract

“…Recent data have shown that the mechanisms involved in the process of nuclear foci formation include association of the HR proteins and the damaged chromatin to the underlying nuclear substructures. Sub-cellular fractionation experiments have shown that after treatment with ionizing radiation and DNA crosslinking agents Rad51, Rad54, BRCA1, BRCA2, FA proteins, and the BLM helicase were associated with the nuclear matrix fraction (Bischof et al, 2001;Qiao et al, 2001;Atanassov et al, 2005;Huber and Chodosh, 2005;Mladenov et al, 2006). The association of Rad51 with the nuclear matrix correlated with the formation of Rad51 nuclear foci and fractionation in situ confirmed that Rad51 foci remained firmly immobilized at the matrix (Mladenov et al, 2006).…”

Section: Discussionmentioning

confidence: 69%

Activation of the S phase DNA damage checkpoint by mitomycin C

Mladenov

Tsaneva

Anachkova

2006

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Aggregation may prevent access to structures such as the nuclear matrix that may be required for repair (Mauldin et al, 2002;Atanassov et al, 2005). However, it is also possible that a delay in repair might accelerate aggregation, and clarification of the relationship between aggregation and repair awaits future study.…”

Section: Discussionmentioning

confidence: 95%

Nonselective DNA damage induced by a replication inhibitor results in the selective elimination of extrachromosomal double minutes from human cancer cells

Shimizu

Misaka

Utani

2007

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Gene amplification plays a pivotal role in human malignancy. Highly amplified genes frequently localize to extrachromosomal double minutes (dmin), which usually segregate to daughter cells in association with mitotic chromosomes. We and others had shown that treatment with low-dose hydroxyurea (HU) results in the elimination of dmin and reversion of the cancer cell phenotype. HU treatment in early S-phase, when dmin are replicated, results in their detachment from chromosomes at the next M-phase, leading to the appearance of micronuclei enriched in dmin, followed by their elimination. In this article, we examined the effect of low-dose HU on the behavior of dmin in relation to DNA damage induction by simultaneously monitoring LacO-tagged dmin and phosphorylated histone H2AX (gammaH2AX). As expected, treatment with low-dose HU induced numerous gammaH2AX foci throughout the nucleus in early S-phase, and these rarely coincided with dmin. Most chromosomal gammaH2AX foci disappeared by metaphase, whereas, unexpectedly, those that persisted frequently associated with dmin. We found that these dmin aggregated, detached from anaphase chromosomes, and apparently formed micronuclei. Because gammaH2AX foci likely represent DNA double strand breaks (DSBs), the response to DSBs sustained by extrachromosomal dmin appears to be different from that sustained by chromosomal loci, which may explain why DSB-inducing agents cause the selective elimination of dmin.

show abstract

Repair of DNA interstrand crosslinks may take place at the nuclear matrix

Cited by 11 publications

References 52 publications

Initiation of DNA interstrand cross‐link repair in mammalian cells

Initiation of DNA interstrand cross‐link repair in mammalian cells

Activation of the S phase DNA damage checkpoint by mitomycin C

Nonselective DNA damage induced by a replication inhibitor results in the selective elimination of extrachromosomal double minutes from human cancer cells

Contact Info

Product

Resources

About