FANCD2 Hurdles the DNA Interstrand Crosslink
نویسندگان
چکیده
Left unrepaired, DNA interstrand crosslinks represent impassable hurdles for DNA replication, and their removal is a complicated stepwise process involving a variety of enzymes. In a recent paper in Science, Knipscheer et al. (2009) demonstrate that the Fanconi Anemia protein FANCD2 promotes multiple steps of the crosslink repair process.
منابع مشابه
FANCD2 binds CtIP and regulates DNA-end resection during DNA interstrand crosslink repair.
The Fanconi anemia (FA) pathway is critically involved in the maintenance of hematopoietic stem cells and the suppression of carcinogenesis. A key FA protein, FANCD2, is monoubiquitinated and accumulates in chromatin in response to DNA interstrand crosslinks (ICLs), where it coordinates DNA repair through mechanisms that are still poorly understood. Here, we report that CtIP protein directly in...
متن کاملFanconi anemia (FA)-associated proteins FANCF and FANCD2 are important components of the FA pathway of DNA crosslink repair. FANCF and FANCD2 have been found to be involved in drug-resistant multiple myeloma, ovarian cancer, non-small-cell lung cancer, and head and neck
The Fanconi anemia (FA)-associated proteins FANCF and FANCD2 are important components of the FA pathway of DNA crosslink repair. FANCF and FANCD2 have been found to be involved in drug-resistant multiple myeloma, ovarian cancer, non-small-cell lung cancer, and head and neck cancer. However, it is unclear whether these two genes participate in adriamycin (ADR)-resistant leukemia. Therefore, the ...
متن کاملCelastrol induces proteasomal degradation of FANCD2 to sensitize lung cancer cells to DNA crosslinking agents
The Fanconi anemia (FA) pathway plays a key role in interstrand crosslink (ICL) repair and maintenance of the genomic stability, while inhibition of this pathway may sensitize cancer cells to DNA ICL agents and ionizing radiation (IR). The active FA core complex acts as an E3 ligase to monoubiquitinate FANCD2, which is a functional readout of an activated FA pathway. In the present study, we ai...
متن کاملHistone chaperone activity of Fanconi anemia proteins, FANCD2 and FANCI, is required for DNA crosslink repair.
Fanconi anaemia (FA) is a rare hereditary disorder characterized by genomic instability and cancer susceptibility. A key FA protein, FANCD2, is targeted to chromatin with its partner, FANCI, and plays a critical role in DNA crosslink repair. However, the molecular function of chromatin-bound FANCD2-FANCI is still poorly understood. In the present study, we found that FANCD2 possesses nucleosome...
متن کاملThe FA Core Complex Contains a Homo-dimeric Catalytic Module for the Symmetric Mono-ubiquitination of FANCI-FANCD2
Activation of the main DNA interstrand crosslink repair pathway in higher eukaryotes requires mono-ubiquitination of FANCI and FANCD2 by FANCL, the E3 ligase subunit of the Fanconi anemia core complex. FANCI and FANCD2 form a stable complex; however, the molecular basis of their ubiquitination is ill defined. FANCD2 mono-ubiquitination by FANCL is stimulated by the presence of the FANCB and FAA...
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عنوان ژورنال:
- Cell
دوره 139 شماره
صفحات -
تاریخ انتشار 2009