Ribonucleotide reductase small subunit p53R2 facilitates p21 induction of G1 arrest under UV irradiation.
p53R2, which is one of the two known ribonucleotide reductase small subunits (the other being M2), is suggested to play an important role in supplying deoxynucleotide triphosphates (dNTP) for DNA repair during the G(1) or G(2) phase of the cell cycle. The ability of p53R2 to supply dNTPs for repairing DNA damages requires the presence of a functional p53 tumor suppressor. Here, we report in vivo physical interaction and colocalization of p53R2 and p21 before DNA damage. Mammalian two-hybrid assay further indicates that the amino acids 1 to 113 of p53R2 are critical for interacting with the NH(2)-terminal region (amino acids 1-93) of p21. The binding between p21 and p53R2 decreases inside the nucleus in response to UV, the time point of which corresponds to the increased binding of p21 with cyclin-dependent kinase-2 (Cdk2), and the decreased Cdk2 activity in the nucleus at G(1). Interestingly, p53R2 dissociates from p21 but facilitates the accumulation of p21 in the nucleus in response to UV. On the other hand, the ribonucleotide reductase activity increases at the corresponding time in response to UV. These data suggest a new function of p53R2 of cooperating with p21 during DNA repair at G(1) arrest.
Xue
Lijun
L
Department of Clinical and Molecular Pharmacology, City of Hope National Medical Center, Duarte, CA 91010, USA.
Zhou
Bingsen
B
Liu
Xiyong
X
Heung
Yvonne
Y
Chau
Jennifer
J
Chu
Emilie
E
Li
Shan
S
Jiang
Chunglin
C
Un
Frank
F
Yen
Yun
Y
D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis* / Q000235:genetics; D004249:DNA Damage / Q000502:physiology*; D004273:DNA, Neoplasm / Q000528:radiation effects; D016193:G1 Phase / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D007624:KB Cells; D011485:Protein Binding; D012264:Ribonucleotide Reductases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014162:Transfection
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004273:DNA, Neoplasm; C405947:RRM2B protein, human; D012264:Ribonucleotide Reductases