Orchestrating the nucleases involved in DNA interstrand cross-link (ICL) repair

Sengerová, Blanka; Wang, Anderson T.; McHugh, Peter J.

doi:10.4161/cc.10.23.18385

Cited by 54 publications

(51 citation statements)

References 108 publications

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“…The ESCRT-II complex is involved in the degradation of both endocytosed EGF and EGFR. EME1, another gene showing greater than additive effect with ERBB2, encodes a protein that is part of an endonuclease complex and may be involved in DNA damage repair and maintaining genomic stability (Sengerov a et al 2011). Other druggable candidate targets on 17q21.3 include UBE2Z, an ubiquitin ligase, and KAT7 (previously known as MYST2), a histone acetyltransferase, both of which showed an additive effect.…”

Section: Discussionmentioning

confidence: 99%

Systems consequences of amplicon formation in human breast cancer

et al. 2014

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Chromosomal structural variations play an important role in determining the transcriptional landscape of human breast cancers. To assess the nature of these structural variations, we analyzed eight breast tumor samples with a focus on regions of gene amplification using mate-pair sequencing of long-insert genomic DNA with matched transcriptome profiling. We found that tandem duplications appear to be early events in tumor evolution, especially in the genesis of amplicons. In a detailed reconstruction of events on chromosome 17, we found large unpaired inversions and deletions connect a tandemly duplicated ERBB2 with neighboring 17q21.3 amplicons while simultaneously deleting the intervening BRCA1 tumor suppressor locus. This series of events appeared to be unusually common when examined in larger genomic data sets of breast cancers albeit using approaches with lesser resolution. Using siRNAs in breast cancer cell lines, we showed that the 17q21.3 amplicon harbored a significant number of weak oncogenes that appeared consistently coamplified in primary tumors. Down-regulation of BRCA1 expression augmented the cell proliferation in ERBB2-transfected human normal mammary epithelial cells. Coamplification of other functionally tested oncogenic elements in other breast tumors examined, such as RIPK2 and MYC on chromosome 8, also parallel these findings. Our analyses suggest that structural variations efficiently orchestrate the gain and loss of cancer gene cassettes that engage many oncogenic pathways simultaneously and that such oncogenic cassettes are favored during the evolution of a cancer.

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Section: Discussionmentioning

confidence: 99%

Systems consequences of amplicon formation in human breast cancer

et al. 2014

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“…Inhibition of ICL repair could promote a transient DSB intermediate by endonucleases (41) such as Mus81-Eme1 (42). In the accepted ICL repair mechanism, the ICL is first unhooked to form a single-stranded DNA with an overhang that was the ICL.…”

Section: Discussionmentioning

confidence: 99%

A Small Molecule Inhibitor of Monoubiquitinated Proliferating Cell Nuclear Antigen (PCNA) Inhibits Repair of Interstrand DNA Cross-link, Enhances DNA Double Strand Break, and Sensitizes Cancer Cells to Cisplatin

Inoue

Kikuchi

Hishiki

et al. 2014

Journal of Biological Chemistry

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Background: Lys-164-monoubiquitinated PCNA is essential for interstrand DNA cross-link (ICL) repair. Results: A small molecule, T2AA, bi-molecularly binds to PCNA at a PIP-box cavity and close to Lys-164. T2AA inhibited monoubiquitinated PCNA interactions and ICL repair and enhanced DNA double strand breaks. Conclusion: An inhibitor of monoubiquitinated PCNA inhibits ICL repair. Significance: Inhibition of monoubiquitinated PCNA could improve chemotherapeutic efficacy.

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“…Each of these nucleases possesses a substrate specificity consistent with a role in the unhooking and removal of ICLs. 87,88 Recent studies involving the use of Xenopus cell-free extracts have provided biochemical evidence for a major role of XPF-ERCC1-SLX4 in ICL removal. 89 FAN1, which possesses 59 flap endonuclease and 59 exonuclease activities, was recently identified as a binding partner of monoubiquitinated FANCD2.…”

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confidence: 99%

Stress and DNA repair biology of the Fanconi anemia pathway

Longerich

Xiong

et al. 2014

Blood

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Fanconi anemia (FA) represents a paradigm of rare genetic diseases, where the quest for cause and cure has led to seminal discoveries in cancer biology. Although a total of 16 FA genes have been identified thus far, the biochemical function of many of the FA proteins remains to be elucidated. FA is rare, yet the fact that 5 FA genes are in fact familial breast cancer genes and FA gene mutations are found frequently in sporadic cancers suggest wider applicability in hematopoiesis and oncology. Establishing the interaction network involving the FA proteins and their associated partners has revealed an intersection of FA with several DNA repair pathways, including homologous recombination, DNA mismatch repair, nucleotide excision repair, and translesion DNA synthesis. Importantly, recent studies have shown a major involvement of the FA pathway in the tolerance of reactive aldehydes. Moreover, despite improved outcomes in stem cell transplantation in the treatment of FA, many challenges remain in patient care. (Blood.

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Orchestrating the nucleases involved in DNA interstrand cross-link (ICL) repair

Cited by 54 publications

References 108 publications

Systems consequences of amplicon formation in human breast cancer

Systems consequences of amplicon formation in human breast cancer

A Small Molecule Inhibitor of Monoubiquitinated Proliferating Cell Nuclear Antigen (PCNA) Inhibits Repair of Interstrand DNA Cross-link, Enhances DNA Double Strand Break, and Sensitizes Cancer Cells to Cisplatin

Stress and DNA repair biology of the Fanconi anemia pathway

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