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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.
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页码:637 / 648
页数:12
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