Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN

Definition:

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). Plays a role in double-strand break repair after gamma-irradiation.

References:

[1]. Sarah A Compton, et al. The Werner syndrome protein binds replication fork and holliday junction DNAs as an oligomer. J Biol Chem. 2008 Sep 5;283(36):24478-83. [Content Brief]

[2]. Patricia L Opresko, et al. The Werner syndrome helicase/exonuclease processes mobile D-loops through branch migration and degradation. PLoS One. 2009;4(3):e4825. [Content Brief]

[3]. Ashwini S Kamath-Loeb, et al. Werner syndrome protein interacts functionally with translesion DNA polymerases. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10394-9. [Content Brief]

[4]. Gabrielle J Grundy, et al. The Ku-binding motif is a conserved module for recruitment and stimulation of non-homologous end-joining proteins. Nat Commun. 2016 Apr 11;7:11242. [Content Brief]

[5]. Alma Zecevic, et al. WRN helicase promotes repair of DNA double-strand breaks caused by aberrant mismatch repair of chromium-DNA adducts. Cell Cycle. 2009 Sep 1;8(17):2769-78. [Content Brief]

[6]. Yu Xue, et al. A minimal exonuclease domain of WRN forms a hexamer on DNA and possesses both 3'- 5' exonuclease and 5'-protruding strand endonuclease activities. Biochemistry. 2002 Mar 5;41(9):2901-12. [Content Brief]

[7]. Jilai Liu, et al. Promyelocytic leukemia protein interacts with werner syndrome helicase and regulates double-strand break repair in γ-irradiation-induced DNA damage responses. Biochemistry (Mosc). 2011 May;76(5):550-4. [Content Brief]

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