Moldovan George-Lucian, D'Andrea Alan D
Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Annu Rev Genet. 2009;43:223-49. doi: 10.1146/annurev-genet-102108-134222.
Fanconi Anemia (FA) is an inherited genomic instability disorder, caused by mutations in genes regulating replication-dependent removal of interstrand DNA crosslinks. The Fanconi Anemia pathway is thought to coordinate a complex mechanism that enlists elements of three classic DNA repair pathways, namely homologous recombination, nucleotide excision repair, and mutagenic translesion synthesis, in response to genotoxic insults. To this end, the Fanconi Anemia pathway employs a unique nuclear protein complex that ubiquitinates FANCD2 and FANCI, leading to formation of DNA repair structures. Lack of obvious enzymatic activities among most FA members has made it challenging to unravel its precise modus operandi. Here we review the current understanding of how the Fanconi Anemia pathway components participate in DNA repair and discuss the mechanisms that regulate this pathway to ensure timely, efficient, and correct restoration of chromosomal integrity.
范可尼贫血（FA）是一种遗传性基因组不稳定疾病，由调节复制依赖性去除链间DNA交联的基因突变引起。范可尼贫血通路被认为可协调一种复杂机制，该机制在响应基因毒性损伤时，会招募三种经典DNA修复通路的元件，即同源重组、核苷酸切除修复和诱变跨损伤合成。为此，范可尼贫血通路利用一种独特的核蛋白复合物，该复合物使FANCD2和FANCI泛素化，从而导致DNA修复结构的形成。大多数FA成员缺乏明显的酶活性，这使得阐明其精确的作用方式具有挑战性。在此，我们综述了目前对范可尼贫血通路成分如何参与DNA修复的理解，并讨论了调节该通路以确保及时、高效和正确恢复染色体完整性的机制。
