title: Checkpoints meet the transcription at a novel histone milestone (H3-T11).
abstract: Eukaryotic cells are equipped with coordinated systems to contend with DNA damage, such as those which are used in cell cycle arrest, DNA repair and apoptosis, to maintain genomic integrity. These systems are regulated at least in part by transcriptional activation or repression. Although processes to activate transcription of specific genes have been characterized in the context of sequence-specific DNA binding factors, mechanisms of transcriptional repression have been largely unexplored. Recently, we identified phosphorylation of histone H3-threonine 11 (H3-T11), a novel chromatin modification for transcriptional activation, that was rapidly reduced after DNA damage. Intriguingly, checkpoint kinase 1 (Chk1) binds to chromatin and phosphorylates H3-T11 under unperturbed conditions. DNA-damage-induced Chk1 dissociation from chromatin closely correlates with decreased phosphorylation of H3-T11. Loss of H3-T11 phosphorylation results in decreased binding of GCN5 with H3, leading to reduced H3-K9 acetylation and transcriptional inhibition. From our results, we have begun to unravel the biological functions of H3-T11 phosphorylation and have uncovered a novel mechanism underlying transcriptional repression in response to DNA damage.
authors.affiliation: Department of Biochemistry and Cell Biology, Medical school, Nagoya City University, Mizuho-ku, Nagoya, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Shimada
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakanishi
mesh_terms: D000071877:Checkpoint Kinase 1; D002843:Chromatin / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D013912:Threonine / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; D013912:Threonine; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1