Tripartite Motif-containing 33 (TRIM33) protein functions in the poly(ADP-ribose) polymerase (PARP)-dependent DNA damage response through interaction with Amplified in Liver Cancer 1 (ALC1) protein.
Activation of poly(ADP-ribose) polymerase (PARP) near sites of DNA breaks facilitates recruitment of DNA repair proteins and promotes chromatin relaxation in part through the action of chromatin-remodeling enzyme Amplified in Liver Cancer 1 (ALC1). Through proteomic analysis we find that ALC1 interacts after DNA damage with Tripartite Motif-containing 33 (TRIM33), a multifunctional protein implicated in transcriptional regulation, TGF-β signaling, and tumorigenesis. We demonstrate that TRIM33 is dynamically recruited to DNA damage sites in a PARP1- and ALC1-dependent manner. TRIM33-deficient cells show enhanced sensitivity to DNA damage and prolonged retention of ALC1 at sites of DNA breaks. Conversely, overexpression of TRIM33 alleviates the DNA repair defects conferred by ALC1 overexpression. Thus, TRIM33 plays a role in PARP-dependent DNA damage response and regulates ALC1 activity by promoting its timely removal from sites of DNA damage.
From the Department of Medicine, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey 08903.
Atul
A
Kulkarni
From the Department of Medicine, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey 08903.
Jay
J
Oza
From the Department of Medicine, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey 08903.
Ming
M
Yao
From the Department of Medicine, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey 08903.
Honeah
H
Sohail
From the Department of Medicine, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey 08903.
Vasudeva
V
Ginjala
the DNA Damage Response Laboratory, London Research Institute, Clare Hall, South Mimms, EN6 3LD Herts, United Kingdom.
Antonia
A
Tomas-Loba
the DNA Damage Response Laboratory, London Research Institute, Clare Hall, South Mimms, EN6 3LD Herts, United Kingdom.
Zuzana
Z
Horejsi
From the Department of Medicine, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey 08903.
Antoinette R
AR
Tan
the DNA Damage Response Laboratory, London Research Institute, Clare Hall, South Mimms, EN6 3LD Herts, United Kingdom.
Simon J
SJ
Boulton
From the Department of Medicine, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey 08903. Electronic address: ganesash@umdnj.edu.
Shridar
S
Ganesan
D000818:Animals; D053960:DNA Breaks; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C511956:TRIM33 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C491420:Trim33 protein, mouse; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D004265:DNA Helicases; C543585:CHD1L protein, human; C546393:Chd1l protein, mouse
ALC1; ATPases; Cancer Biology; Cell Signaling; Chromatin; DNA Damage Response; PARP; TRIM33