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SQ/TQ cluster domains: concentrated ATM/ATR kinase phosphorylation site regions in DNA‐damage‐response proteins
Author(s) -
Traven Ana,
Heierhorst Jörg
Publication year - 2005
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.20204
Subject(s) - phosphorylation , dna damage , kinase , dna , microbiology and biotechnology , biology , dna damage repair , dna binding protein , dna repair , biochemistry , chemistry , genetics , gene , transcription factor
Abstract ATM/ATR‐like protein kinases play central roles in the maintenance of genome stability and phosphorylate numerous substrates in response to DNA damage, preferentially on SQ or TQ motifs. ATM/ATR substrates often contain several closely spaced SQ/TQ motifs in regions that have been termed SQ/TQ cluster domains (SCDs). SCDs are now considered a structural hallmark of DNA‐damage‐response proteins. Mutational analyses of a number of SCD‐containing proteins indicate that multisite phosphorylation of SQ/TQ motifs is required for normal DNA‐damage responses, most commonly by mediating protein–protein interactions in the formation of DNA‐damage‐induced complexes. SCD sequences are highly diverse and these domains may be largely unfolded in their native state rather than adopting a common three‐dimensional fold. Structural disorder of SCDs could be advantageous for efficient phosphorylation by ATM/ATR kinases and also enable them to be molded into distinct conformations to facilitate flexible interactions with multiple binding partners. BioEssays 27:397–407, 2005. © 2005 Wiley periodicals, Inc.