3aaf
From Proteopedia
Structure of WRN RQC domain bound to double-stranded DNA
Structural highlights
Disease[WRN_HUMAN] Defects in WRN are a cause of Werner syndrome (WRN) [MIM:277700]. WRN is a rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus, ocular cataracts and osteoporosis. The major cause of death, at a median age of 47, is myocardial infarction. Currently all known WS mutations produces prematurely terminated proteins.[1] Defects in WRN may be a cause of colorectal cancer (CRC) [MIM:114500]. Function[WRN_HUMAN] Multifunctional enzyme that has both magnesium and ATP-dependent DNA-helicase activity and 3'->5' exonuclease activity towards double-stranded DNA with a 5'-overhang. Has no nuclease activity towards single-stranded DNA or blunt-ended double-stranded DNA. Binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and Holliday junctions. May play an important role in the dissociation of joint DNA molecules that can arise as products of homologous recombination, at stalled replication forks or during DNA repair. Alleviates stalling of DNA polymerases at the site of DNA lesions. Important for genomic integrity. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A (By similarity).[2] [3] [4] [5] [6] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe RecQ family of DNA helicases including WRN (Werner syndrome protein) and BLM (Bloom syndrome protein) protects the genome against deleterious changes. Here we report the cocrystal structure of the RecQ C-terminal (RQC) domain of human WRN bound to a DNA duplex. In the complex, the RQC domain specifically interacted with a blunt end of the duplex and, surprisingly, unpaired a Watson-Crick base pair in the absence of an ATPase domain. The beta wing, an extended hairpin motif that is characteristic of winged-helix motifs, was used as a "separating knife" to wedge between the first and second base pairs, whereas the recognition helix, a principal component of helix-turn-helix motifs that are usually embedded within DNA grooves, was unprecedentedly excluded from the interaction. Our results demonstrate a function of the winged-helix motif central to the helicase reaction, establishing the first structural paradigm concerning the DNA structure-specific activities of the RecQ helicases. Structural basis for DNA strand separation by the unconventional winged-helix domain of RecQ helicase WRN.,Kitano K, Kim SY, Hakoshima T Structure. 2010 Feb 10;18(2):177-87. PMID:20159463[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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