Cellular response to DNA interstrand crosslinks: the Fanconi anemia pathway.
Interstrand crosslinks (ICLs) are a highly toxic form of DNA damage. ICLs can interfere with vital biological processes requiring separation of the two DNA strands, such as replication and transcription. If ICLs are left unrepaired, it can lead to mutations, chromosome breakage and mitotic catastrophe. The Fanconi anemia (FA) pathway can repair this type of DNA lesion, ensuring genomic stability. In this review, we will provide an overview of the cellular response to ICLs. First, we will discuss the origin of ICLs, comparing various endogenous and exogenous sources. Second, we will describe FA proteins as well as FA-related proteins involved in ICL repair, and the post-translational modifications that regulate these proteins. Finally, we will review the process of how ICLs are repaired by both replication-dependent and replication-independent mechanisms.
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
David
D
Lopez-Martinez
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
Chih-Chao
CC
Liang
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK. martin.cohn@bioch.ox.ac.uk.
Martin A
MA
Cohn
D000818:Animals; D003432:Cross-Linking Reagents / Q000009:adverse effects*; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018736:DNA Adducts / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair; D004261:DNA Replication; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics / Q000378:metabolism*; D042822:Genomic Instability; D006801:Humans; D007364:Intercalating Agents / Q000009:adverse effects; D008958:Models, Molecular; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
D003432:Cross-Linking Reagents; D018736:DNA Adducts; D051856:Fanconi Anemia Complementation Group Proteins; D007364:Intercalating Agents; D004247:DNA
DNA repair; FANCD2; FANCI; Genomic instability; Phosphorylation; SUMO; UHRF1; Ubiquitination