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Dna2 on the road to Okazaki fragment processing and genome stability in eukaryotes.

Authors
Type
Published Article
Journal
Critical Reviews in Biochemistry and Molecular Biology
1549-7798
Publisher
Informa UK (Taylor & Francis)
Publication Date
Volume
45
Issue
2
Pages
71–96
Identifiers
DOI: 10.3109/10409230903578593
PMID: 20131965
Source
Medline
License
Unknown

Abstract

DNA replication is a primary mechanism for maintaining genome integrity, but it serves this purpose best by cooperating with other proteins involved in DNA repair and recombination. Unlike leading strand synthesis, lagging strand synthesis has a greater risk of faulty replication for several reasons: First, a significant part of DNA is synthesized by polymerase alpha, which lacks a proofreading function. Second, a great number of Okazaki fragments are synthesized, processed and ligated per cell division. Third, the principal mechanism of Okazaki fragment processing is via generation of flaps, which have the potential to form a variety of structures in their sequence context. Finally, many proteins for the lagging strand interact with factors involved in repair and recombination. Thus, lagging strand DNA synthesis could be the best example of a converging place of both replication and repair proteins. To achieve the risky task with extraordinary fidelity, Okazaki fragment processing may depend on multiple layers of redundant, but connected pathways. An essential Dna2 endonuclease/helicase plays a pivotal role in processing common structural intermediates that occur during diverse DNA metabolisms (e.g. lagging strand synthesis and telomere maintenance). Many roles of Dna2 suggest that the preemptive removal of long or structured flaps ultimately contributes to genome maintenance in eukaryotes. In this review, we describe the function of Dna2 in Okazaki fragment processing, and discuss its role in the maintenance of genome integrity with an emphasis on its functional interactions with other factors required for genome maintenance.

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