SQ/TQ cluster domains: Concentrated ATM/ATR kinase phosphorylation site regions in DNA-damage-response proteins

Ana Traven, Jorg Heierhorst

Research output: Contribution to journalReview ArticleResearchpeer-review

138 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)397 - 407
Number of pages11
JournalBioEssays
Volume27
Issue number4
DOIs
Publication statusPublished - 2005
Externally publishedYes

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