Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase.
A balanced deoxyribonucleotide (dNTP) supply is essential for DNA repair. Here, we found that ribonucleotide reductase (RNR) subunits RRM1 and RRM2 accumulated very rapidly at damage sites. RRM1 bound physically to Tip60. Chromatin immunoprecipitation analyses of cells with an I-SceI cassette revealed that RRM1 bound to a damage site in a Tip60-dependent manner. Active RRM1 mutants lacking Tip60 binding failed to rescue an impaired DNA repair in RRM1-depleted G1-phase cells. Inhibition of RNR recruitment by an RRM1 C-terminal fragment sensitized cells to DNA damage. We propose that Tip60-dependent recruitment of RNR plays an essential role in dNTP supply for DNA repair.
Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University Medical School, Nagoya 467-8601, Japan.
Hiroyuki
H
Niida
Yuko
Y
Katsuno
Misuzu
M
Sengoku
Midori
M
Shimada
Megumi
M
Yukawa
Masae
M
Ikura
Tsuyoshi
T
Ikura
Kazuteru
K
Kohno
Hiroki
H
Shima
Hidekazu
H
Suzuki
Satoshi
S
Tashiro
Makoto
M
Nakanishi
D000818:Animals; D004249:DNA Damage / Q000502:physiology*; D016193:G1 Phase / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D051379:Mice; D012264:Ribonucleotide Reductases / Q000378:metabolism*; D015534:Trans-Activators
D015534:Trans-Activators; D012264:Ribonucleotide Reductases; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; C523065:Kat5 protein, mouse; D000074443:Lysine Acetyltransferase 5