Structure and function of Cdc6/Cdc18: Implications for origin recognition and checkpoint control

被引:183
作者
Liu, JY [1 ]
Smith, CL [1 ]
DeRyckere, D [1 ]
DeAngelis, K [1 ]
Martin, GS [1 ]
Berger, JM [1 ]
机构
[1] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA
关键词
D O I
10.1016/S1097-2765(00)00062-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cdc6/Cdc18 is a conserved and essential component of prereplication complexes. The 2.0 Angstrom crystal structure of an archaeal Cdc6 ortholog, in conjunction with a mutational analysis of the homologous Cdc18 protein from Schizosaccharomyces pombe, reveals novel aspects of Cdc6/Cdc18 function. Two domains of Cdc6 form an AAA(+)-type nucleotide binding fold that is observed bound to Mg ADP. A third domain adopts a winged-helix fold similar to known DNA binding modules. Sequence comparisons show that the winged-helix domain is conserved in Orc1, and mutagenesis data demonstrate that this region of Cdc6/Cdc18 is required for function in vivo. Additional mutational analyses suggest that nucleotide binding and/or hydrolysis by Cdc6/Cdc18 is required not only for progression through S phase, but also for maintenance of checkpoint control during S phase.
引用
收藏
页码:637 / 648
页数:12
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