4DAY

Crystal structure of the RMI core complex with MM2 peptide from FANCM

Summary for 4DAY

• Entry DOI: 10.2210/pdb4day/pdb
• Related: 3MXN 3NBH
• Descriptor: RecQ-mediated genome instability protein 1, RecQ-mediated genome instability protein 2, Fanconi anemia group M protein (3 entities in total)
• Functional Keywords: ob fold, protein binding-hydrolase complex, protein binding/hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : Q9H9A7 Q96E14 Q8IYD8
• Total number of polymer chains: 3
• Total formula weight: 37769.29

Authors

Hoadley, K.A.,Keck, J.L. (deposition date: 2012-01-13, release date: 2012-03-14, Last modification date: 2023-09-13)

Primary citation

Hoadley, K.A.,Xue, Y.,Ling, C.,Takata, M.,Wang, W.,Keck, J.L.
Defining the molecular interface that connects the Fanconi anemia protein FANCM to the Bloom syndrome dissolvasome.
Proc.Natl.Acad.Sci.USA, 109:4437-4442, 2012

PubMed Abstract: The RMI subcomplex (RMI1/RMI2) functions with the BLM helicase and topoisomerase IIIα in a complex called the "dissolvasome," which separates double-Holliday junction DNA structures that can arise during DNA repair. This activity suppresses potentially harmful sister chromatid exchange (SCE) events in wild-type cells but not in cells derived from Bloom syndrome patients with inactivating BLM mutations. The RMI subcomplex also associates with FANCM, a component of the Fanconi anemia (FA) core complex that is important for repair of stalled DNA replication forks. The RMI/FANCM interface appears to help coordinate dissolvasome and FA core complex activities, but its precise role remains poorly understood. Here, we define the structure of the RMI/FANCM interface and investigate its roles in coordinating cellular DNA-repair activities. The X-ray crystal structure of the RMI core complex bound to a well-conserved peptide from FANCM shows that FANCM binds to both RMI proteins through a hydrophobic "knobs-into-holes" packing arrangement. The RMI/FANCM interface is shown to be critical for interaction between the components of the dissolvasome and the FA core complex. FANCM variants that substitute alanine for key interface residues strongly destabilize the complex in solution and lead to increased SCE levels in cells that are similar to those observed in blm- or fancm-deficient cells. This study provides a molecular view of the RMI/FANCM complex and highlights a key interface utilized in coordinating the activities of two critical eukaryotic DNA-damage repair machines.

PubMed: 22392978
DOI: 10.1073/pnas.1117279109

Experimental method

X-RAY DIFFRACTION (3.3 Å)