Mec1/Tel1 phosphorylation of the INO80 chromatin remodeling complex influences DNA damage checkpoint responses.
The yeast Mec1/Tel1 kinases, ATM/ATR in mammals, coordinate the DNA damage response by phosphorylating proteins involved in DNA repair and checkpoint pathways. Recently, ATP-dependent chromatin remodeling complexes, such as the INO80 complex, have also been implicated in DNA damage responses, although regulatory mechanisms that direct their function remain unknown. Here, we show that the Ies4 subunit of the INO80 complex is phosphorylated by the Mec1/Tel1 kinases during exposure to DNA-damaging agents. Mutation of Ies4's phosphorylation sites does not significantly affect DNA repair processes, but does influence DNA damage checkpoint responses. Additionally, ies4 phosphorylation mutants are linked to the function of checkpoint regulators, such as the replication checkpoint factors Tof1 and Rad53. These findings establish a chromatin remodeling complex as a functional component in the Mec1/Tel1 DNA damage signaling pathway that modulates checkpoint responses and suggest that posttranslational modification of chromatin remodeling complexes regulates their involvement in distinct processes.
Morrison
Ashby J
AJ
Department of Carcinogenesis, Science Park Research Division, University of Texas M.D. Anderson Cancer Center, Smithville, TX 78957, USA.
Kim
Jung-Ae
JA
Person
Maria D
MD
Highland
Jessica
J
Xiao
Jing
J
Wehr
Tammy S
TS
Hensley
Sean
S
Bao
Yunhe
Y
Shen
Jianjun
J
Collins
Sean R
SR
Weissman
Jonathan S
JS
Delrow
Jeff
J
Krogan
Nevan J
NJ
Haber
James E
JE
Shen
Xuetong
X
D002453:Cell Cycle / Q000502:physiology*; D002843:Chromatin / Q000502:physiology*; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D002843:Chromatin; C483404:INO80 complex, S cerevisiae; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C513623:TEL1 protein, S cerevisiae