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Regulation of the Rhp26ERCC6/CSB chromatin remodeler by a novel conserved leucine latch motif

Wang, Lanfeng
; 
Limbo, Oliver
; 
Fei, Jia
; ; 
Kim, Bong
; 
Luo, Jie
; 
Chong, Jenny
; 
Conaway, Ronald C.
; 
Conaway, Joan W.
; 
Ranish, Jeff A.
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Post-print
Date
2014-12-15
Advisor
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Lu Chen Lab (Temple University)
Fox Chase Cancer Center
Department
Cancer and Cellular Biology
Subject
Chromatin remodeling
 SWI2/SNF2
 SNF2-like family ATPase
 Enzyme autoregulation
 Flanking regions
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http://hdl.handle.net/20.500.12613/9100
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DOI
https://doi.org/10.1073/pnas.1420227112
Abstract
CSB/ERCC6 (Cockayne syndrome B protein/excision repair cross-complementation group 6), a member of a subfamily of SWI2/SNF2 (SWItch/sucrose nonfermentable)-related chromatin remodelers, plays crucial roles in gene expression and the maintenance of genome integrity. Here, we report the mechanism of the autoregulation of Rhp26, which is the homolog of CSB/ERCC6 in Schizosaccharomyces pombe. We identified a novel conserved protein motif, termed the “leucine latch,” at the N terminus of Rhp26. The leucine latch motif mediates the autoinhibition of the ATPase and chromatin-remodeling activities of Rhp26 via its interaction with the core ATPase domain. Moreover, we found that the C terminus of the protein counteracts this autoinhibition and that both the N- and C-terminal regions of Rhp26 are needed for its proper function in DNA repair in vivo. The presence of the leucine latch motif in organisms ranging from yeast to humans suggests a conserved mechanism for the autoregulation of CSB/ERCC6 despite the otherwise highly divergent nature of the N- and C-terminal regions.
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Citation
Wang L, Limbo O, Fei J, Chen L, Kim B, Luo J, et al. Regulation of the Rhp26ERCC6/CSB chromatin remodeler by a novel conserved leucine latch motif. Proc. Natl. Acad. Sci. 2014 Dec 15;111(52):18566–71. doi:10.1073/pnas.1420227112.
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© 2014 National Academy of Sciences.
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Proceedings of the National Academy of Sciences (PNAS), Vol. 111, No. 52
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