TY - JOUR
T1 - ATR homolog Mec1 controls association of DNA polymerase ζ-Rev1 complex with regions near a double-strand break
AU - Hirano, Yukinori
AU - Sugimoto, Katsunori
N1 - Funding Information:
We thank J. Kang and L. Ripley for critical reading; C. Lawrence for materials; and D. Nakada, C. Newlon, and L. Ripley for helpful discussion. This work was supported by grants from National Institutes of Health (NIH GM073876) and the University of Medicine and Dentistry of New Jersey (UMDNJ) foundation.
PY - 2006/3/21
Y1 - 2006/3/21
N2 - DNA polymerase zeta (Polζ) and Rev1 contribute to the bypassing of DNA lesions, termed translesion DNA synthesis (TLS) [1-3]. Polζ consists of two subunits, one encoded by REV3 (the catalytic subunit) and the other encoded by REV7. Rev1 acts as a deoxycytidyl transferase, inserting dCMP opposite lesions. Polζ and Rev1 have been shown to operate in the same TLS pathway in the budding yeast Saccharomyces cerevisiae [2, 3]. Here, we show that budding yeast Polζ and Rev1 form a complex and associate together with double-strand breaks (DSBs). As a component of the Polζ-Rev1 complex, Rev1 plays a noncatalytic role in the association with DSBs. In budding yeast, the ATR-homolog Mec1 plays a central role in the DNA-damage checkpoint response [4, 5]. We further show that Mec1-dependent phosphorylation promotes the Polζ-Rev1 association with DSBs. Rev1 association with DSBs requires neither the function of the Rad24 checkpoint-clamp loader [5] nor the Rad6-Rad18-mediated ubiquitination of PCNA [3]. Our results reveal a novel role of Mec1 in the localization of the Polζ-Rev1 complex to DNA lesions and highlight a linkage of TLS polymerases to the checkpoint response.
AB - DNA polymerase zeta (Polζ) and Rev1 contribute to the bypassing of DNA lesions, termed translesion DNA synthesis (TLS) [1-3]. Polζ consists of two subunits, one encoded by REV3 (the catalytic subunit) and the other encoded by REV7. Rev1 acts as a deoxycytidyl transferase, inserting dCMP opposite lesions. Polζ and Rev1 have been shown to operate in the same TLS pathway in the budding yeast Saccharomyces cerevisiae [2, 3]. Here, we show that budding yeast Polζ and Rev1 form a complex and associate together with double-strand breaks (DSBs). As a component of the Polζ-Rev1 complex, Rev1 plays a noncatalytic role in the association with DSBs. In budding yeast, the ATR-homolog Mec1 plays a central role in the DNA-damage checkpoint response [4, 5]. We further show that Mec1-dependent phosphorylation promotes the Polζ-Rev1 association with DSBs. Rev1 association with DSBs requires neither the function of the Rad24 checkpoint-clamp loader [5] nor the Rad6-Rad18-mediated ubiquitination of PCNA [3]. Our results reveal a novel role of Mec1 in the localization of the Polζ-Rev1 complex to DNA lesions and highlight a linkage of TLS polymerases to the checkpoint response.
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U2 - 10.1016/j.cub.2006.01.063
DO - 10.1016/j.cub.2006.01.063
M3 - Article
C2 - 16546083
AN - SCOPUS:33645008019
VL - 16
SP - 586
EP - 590
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 6
ER -