Evaluating Interstrand Crosslink (ICL) Repair in Triple-Negative Breast Cancers To Guide Chemotherapy
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Interstrand crosslink repair: can XPF-ERCC1 be let off the hook?
The interstrand crosslink (ICL) presents a challenge to both the cell and the scientist. From a clinical standpoint, these lesions are particularly intriguing: ICL-inducing agents are powerful tools in cancer chemotherapy, and spontaneous ICLs have recently been linked with accelerated aging phenotypes. Nevertheless, the ICL repair process has proven difficult to elucidate. Here we discuss rece...
متن کاملRecruitment and positioning determine the specific role of the XPF‐ERCC1 endonuclease in interstrand crosslink repair
XPF-ERCC1 is a structure-specific endonuclease pivotal for several DNA repair pathways and, when mutated, can cause multiple diseases. Although the disease-specific mutations are thought to affect different DNA repair pathways, the molecular basis for this is unknown. Here we examine the function of XPF-ERCC1 in DNA interstrand crosslink (ICL) repair. We used Xenopus egg extracts to measure bot...
متن کاملSynthesis and incorporation of a furan-modified adenosine building block for DNA interstrand crosslinking.
2'-O-(3-(Furan-2-yl)propyl)adenosine was synthesized and evaluated for interstrand crosslink (ICL) formation in DNA duplexes. In situ oxidation of the furan moiety with NIS showed rapid crosslink formation to dA and dC, while dT and dG were inactive.
متن کاملReplication-Fork Stalling and Processing at a Single Psoralen Interstrand Crosslink in Xenopus Egg Extracts
Interstrand crosslink (ICL)-inducing agents block the separation of the two DNA strands. They prevent transcription and replication and are used in clinics for the treatment of cancer and skin diseases. Here, we have introduced a single psoralen ICL at a specific site in plasmid DNA using a triplex-forming-oligonucleotide (TFO)-psoralen conjugate and studied its repair in Xenopus egg extracts t...
متن کاملStrategies for DNA interstrand crosslink repair: insights from worms, flies, frogs, and slime molds.
DNA interstrand crosslinks (ICLs) are complex lesions that covalently link both strands of the DNA double helix and impede essential cellular processes such as DNA replication and transcription. Recent studies suggest that multiple repair pathways are involved in their removal. Elegant genetic analysis has demonstrated that at least three distinct sets of pathways cooperate in the repair and/or...
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