title: Condensin recruitment to chromatin is inhibited by Chk2 kinase in response to DNA damage.
abstract: The DNA damage checkpoint, when activated in response to genotoxic damage during S phase, arrests cells in G2 phase of the cell cycle. ATM, ATR, Chk1 and Chk2 kinases are the main effectors of this checkpoint pathway. The checkpoint kinases prevent the onset of mitosis by eliciting well characterized inhibitory phosphorylation of Cdk1. Since Cdk1 is required for the recruitment of condensin, it is thought that upon DNA damage the checkpoint also indirectly blocks chromosome condensation via Cdk1 inhibition. Here we report that the G2 damage checkpoint prevents stable recruitment of the chromosome-packaging-machinery components condensin complex I and II onto the chromatin even in the presence of an active Cdk1. DNA damage-induced inhibition of condensin subunit recruitment is mediated specifically by the Chk2 kinase, implying that the condensin complexes are targeted by the checkpoint in response to DNA damage, independently of Cdk1 inactivation. Thus, the G2 checkpoint directly prevents stable recruitment of condensin complexes to actively prevent chromosome compaction during G2 arrest, presumably to ensure efficient repair of the genomic damage.
authors: a Institute of Molecular and Cell Biology, Agency for Science Technology and Research , Singapore.|b Murdoch Childrens Research Institute, Royal Children's Hospital , Melbourne , Australia.|c Department of Pediatrics , University of Melbourne, Royal Children's Hospital , Melbourne , Australia.
authors: Tao
authors: T
authors: Zhang
authors: a Institute of Molecular and Cell Biology, Agency for Science Technology and Research , Singapore.
authors: San Ling
authors: SL
authors: Si-Hoe
authors: b Murdoch Childrens Research Institute, Royal Children's Hospital , Melbourne , Australia.|c Department of Pediatrics , University of Melbourne, Royal Children's Hospital , Melbourne , Australia.
authors: Damien F
authors: DF
authors: Hudson
authors: a Institute of Molecular and Cell Biology, Agency for Science Technology and Research , Singapore.|d Department of Pharmacology , National University of Singapore , Singapore.|e Bioprocessing Technology Institute, Agency for Science Technology and Research , Singapore.
authors: Uttam
authors: U
authors: Surana
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2 / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D002877:Chromosomes, Human / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021122:Protein Subunits / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D021122:Protein Subunits; C490381:SMC2 protein, human; C108312:condensin complexes; D004317:Doxorubicin; D064447:Checkpoint Kinase 2; D064007:Ataxia Telangiectasia Mutated Proteins; D000251:Adenosine Triphosphatases
keywords: Cell Cycle; Checkpoint; Chromosome condensation; DNA damage; Mitosis