Constantinou Angelos
Institute of Human Genetics, CNRS UPR 1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France.
Chromosoma. 2012 Feb;121(1):21-36. doi: 10.1007/s00412-011-0349-2. Epub 2011 Nov 6.
Chromosomal aberrations are often associated with incomplete genome duplication, for instance at common fragile sites, or as a consequence of chemical alterations in the DNA template that block replication forks. Studies of the cancer-prone disease Fanconi anaemia (FA) have provided important insights into the resolution of replication problems. The repair of interstrand DNA crosslinks induced by chemotherapy drugs is coupled with DNA replication and controlled by FA proteins. We discuss here the recent discovery of new FA-associated proteins and the development of new tractable repair systems that have dramatically improved our understanding of crosslink repair. We focus also on how FA proteins protect against replication failure in the context of fragile sites and on the identification of reactive metabolites that account for the development of Fanconi anaemia symptoms.
染色体畸变通常与基因组复制不完全有关，例如在常见的脆性位点，或者是由于DNA模板中的化学改变阻碍了复制叉。对易患癌症的范可尼贫血（FA）的研究为解决复制问题提供了重要见解。化疗药物诱导的链间DNA交联的修复与DNA复制相关联，并由FA蛋白控制。我们在此讨论新的FA相关蛋白的最新发现以及新的易处理修复系统的开发，这些发现和开发极大地增进了我们对交联修复的理解。我们还关注FA蛋白如何在脆性位点的背景下防止复制失败，以及对导致范可尼贫血症状发展的反应性代谢物的鉴定。
