title: Orchestrating the nucleases involved in DNA interstrand cross-link (ICL) repair.
abstract: DNA interstrand cross-links (ICLs) pose a significant threat to genomic and cellular integrity by blocking essential cellular processes, including replication and transcription. In mammalian cells, much ICL repair occurs in association with DNA replication during S phase, following the stalling of a replication fork at the block caused by an ICL lesion. Here, we review recent work showing that the XPF-ERCC1 endonuclease and the hSNM1A exonuclease act in the same pathway, together with SLX4, to initiate ICL repair, with the MUS81-EME1 fork incision activity becoming important in the absence of the XPF-SNM1A-SLX4-dependent pathway. Another nuclease, the Fanconi anemia-associated nuclease (FAN1), has recently been implicated in the repair of ICLs, and we discuss the possible ways in which the activities of different nucleases at the ICL-stalled replication fork may be coordinated. In relation to this, we briefly speculate on the possible role of SLX4, which contains XPF and MUS81- interacting domains, in the coordination of ICL repair nucleases.
authors.affiliation: Department of Oncology, Weatherall Institute of Molecular Medicine,University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Blanka
authors.initials: B
authors.lastname: Sengerová
authors.forename: Anderson T
authors.initials: AT
authors.lastname: Wang
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McHugh
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004706:Endodeoxyribonucleases; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D064251:Multifunctional Enzymes; D017434:Protein Structure, Tertiary; D045522:Recombinases / Q000235:genetics / Q000378:metabolism; D018741:Replication Origin; D013329:Structure-Activity Relationship
chemical_list: D004268:DNA-Binding Proteins; D064251:Multifunctional Enzymes; D045522:Recombinases; C095888:xeroderma pigmentosum group F protein; D004247:DNA; C071447:ERCC1 protein, human; D004706:Endodeoxyribonucleases; D004720:Endonucleases; D005090:Exodeoxyribonucleases; C551063:FAN1 protein, human; C498772:MUS81 protein, human; C542319:SLX4 protein, human
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