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4 Roles of Nuclear Structure in DNA Replication

Ronald Laskey, Mark Madine


The cell nucleus is the defining feature of eukaryotes. It is bounded by a nuclear envelope consisting of two concentric layers of membrane perforated by nuclear pores that serve as channels of communication between the nucleus and the cytoplasm. DNA is not randomly packed into the nucleus but packaged precisely in such a way that all regions are accessible for replication each cell cycle. Partial access and therefore partial replication would result in chromosome breakage or nondisjunction at mitosis, with disastrous consequences. The packing hierarchy involves radial loop organization from an axial scaffold, as well as the compaction resulting from coiling DNA twice around the nucleosome subunits of chromatin (Schedl and Grosveld 1995; Van Holde et al. 1995).

A crucial feature of eukaryotic chromosomal DNA replication is that it always occurs within a nucleus. In lower eukaryotes such as fungi or Physarum, the nuclear membrane remains intact throughout the cell cycle, whereas it breaks down during mitosis of higher eukaryotes. Nevertheless, replication is constrained to interphase when the nuclear membrane is intact. We argue that this constraint has important regulatory consequences.

Further key features of eukaryotic DNA replication are that multiple initiations occur within a single chromosome and that these initiations are coordinated so that each region of the chromosome replicates, but replicates only once in any cell cycle. We argue that nuclear structure has essential roles to play in coordinating multiple initiations to replicate the chromosome exactly once.

Studies of eukaryotic...

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