Evolutionary conservation of the CDK targets in eukaryotic DNA replication initiation
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A fundamental requirement for all organisms is the faithful duplication and transmission of the genetic material. Failure to accurately copy and segregate the genome during cell division leads to loss of genetic information and chromosomal abnormalities. Such genome instability is the hallmark of the earliest stages of tumour formation. Cyclin-dependent kinase (CDK) plays a vital role in regulating the duplication of the genome within the eukaryotic cell cycle. Importantly, this kinase is deregulated in many cancer types and is an emerging target of chemotherapeutics. In this review, I will consider recent advances concerning the role of CDK in replication initiation across eukaryotes. The implications for strict CDK-dependent regulation of genome duplication in the context of the cell cycle will be discussed.
KeywordsReplication Initiation Origin Recognition Complex Origin Firing RecQ4 Helicase Rothmund Thomson Syndrome
I apologise for any omissions due to space limitations and I am grateful to anonymous referees for their comments. I thank Vincent Gaggioli for critical reading of the manuscript and Max Telford and the Genome Institute at Washington University for access to the Priapulus caudatus genome sequence. PZ is supported Worldwide Cancer Research (AICR) 10-0908.
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