Dedicated to the core: understanding the Fanconi anemia complex.
The Fanconi anemia (FA) pathway consists of a unique, multi-subunit E3 ubiquitin ligase complex that is activated in a replication and DNA-damage dependent mechanism. This FA core complex possesses a putative helicase and an E3 ubiquitin ligase subunit, is assembled in both the nucleoplasm and in chromatin, and is required for the mono-ubiquitination of FANCD2, a downstream FA protein, following genotoxic stress. Clinically, absence of the FA pathway results in congenital defects, bone marrow failure, and cancer predisposition. At the cellular level, this pathway is required for chromosomal stability and cellular resistance to DNA interstrand crosslinkers (ICLs) such as mitomycin C (MMC). A general model has emerged for the FA pathway as an arm of the DNA-damage response following ICLs. This review will summarize the current understanding of the FA core complex and propose a model for its activity.
Gurtan
Allan M
AM
Biological and Biomedical Sciences Program, Harvard Medical School, Boston, Massachusetts 02115, USA.
D'Andrea
Alan D
AD
D000818:Animals; D002645:Chickens; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D043171:Chromosomal Instability; D004249:DNA Damage; D004261:DNA Replication; D005199:Fanconi Anemia / Q000235:genetics* / Q000378:metabolism; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
D002843:Chromatin; D051856:Fanconi Anemia Complementation Group Proteins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases