title: WDR76 Co-Localizes with Heterochromatin Related Proteins and Rapidly Responds to DNA Damage.
abstract: Proteins that respond to DNA damage play critical roles in normal and diseased states in human biology. Studies have suggested that the S. cerevisiae protein CMR1/YDL156w is associated with histones and is possibly associated with DNA repair and replication processes. Through a quantitative proteomic analysis of affinity purifications here we show that the human homologue of this protein, WDR76, shares multiple protein associations with the histones H2A, H2B, and H4. Furthermore, our quantitative proteomic analysis of WDR76 associated proteins demonstrated links to proteins in the DNA damage response like PARP1 and XRCC5 and heterochromatin related proteins like CBX1, CBX3, and CBX5. Co-immunoprecipitation studies validated these interactions. Next, quantitative imaging studies demonstrated that WDR76 was recruited to laser induced DNA damage immediately after induction, and we compared the recruitment of WDR76 to laser induced DNA damage to known DNA damage proteins like PARP1, XRCC5, and RPA1. In addition, WDR76 co-localizes to puncta with the heterochromatin proteins CBX1 and CBX5, which are also recruited to DNA damage but much less intensely than WDR76. This work demonstrates the chromatin and DNA damage protein associations of WDR76 and demonstrates the rapid response of WDR76 to laser induced DNA damage.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO, 64110, United States of America.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Gilmore
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO, 64110, United States of America.
authors.forename: Mihaela E
authors.initials: ME
authors.lastname: Sardiu
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO, 64110, United States of America.
authors.forename: Brad D
authors.initials: BD
authors.lastname: Groppe
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO, 64110, United States of America.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Thornton
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO, 64110, United States of America.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO, 64110, United States of America.
authors.forename: Gerald
authors.initials: G
authors.lastname: Dayebgadoh
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO, 64110, United States of America.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Banks
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO, 64110, United States of America.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Slaughter
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO, 64110, United States of America.
authors.forename: Jay R
authors.initials: JR
authors.lastname: Unruh
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO, 64110, United States of America.
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Workman
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO, 64110, United States of America.
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO, 64110, United States of America.|Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas, 66160, United States of America.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
mesh_terms: D018797:Cell Cycle Proteins; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004249:DNA Damage; D004268:DNA-Binding Proteins; D057809:HEK293 Cells; D006570:Heterochromatin / Q000378:metabolism*; D006801:Humans
chemical_list: C000715593:CBX1 protein, human; C000715594:CBX5 protein, human; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006570:Heterochromatin; C000606100:WDR76 protein, human; D000090266:Chromobox Protein Homolog 5