Repriming DNA synthesis: an intrinsic restart pathway that maintains efficient genome replication

Bainbridge, Lewis J, Teague, Rebecca and Doherty, Aidan J (2021) Repriming DNA synthesis: an intrinsic restart pathway that maintains efficient genome replication. Nucleic Acids Research, 49 (9). pp. 4831-4847. ISSN 0305-1048

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Abstract

To bypass a diverse range of fork stalling impediments encountered during genome replication, cells possess a variety of DNA damage tolerance (DDT) mechanisms including translesion synthesis, template switching, and fork reversal. These pathways function to bypass obstacles and allow efficient DNA synthesis to be maintained. In addition, lagging strand obstacles can also be circumvented by downstream priming during Okazaki fragment generation, leaving gaps to be filled post-replication. Whether repriming occurs on the leading strand has been intensely debated over the past half-century. Early studies indicated that both DNA strands were synthesised discontinuously. Although later studies suggested that leading strand synthesis was continuous, leading to the preferred semi-discontinuous replication model. However, more recently it has been established that replicative primases can perform leading strand repriming in prokaryotes. An analogous fork restart mechanism has also been identified in most eukaryotes, which possess a specialist primase called PrimPol that conducts repriming downstream of stalling lesions and structures. PrimPol also plays a more general role in maintaining efficient fork progression. Here, we review and discuss the historical evidence and recent discoveries that substantiate repriming as an intrinsic replication restart pathway for maintaining efficient genome duplication across all domains of life.

Item Type: Article
Keywords: Animals, DNA, DNA Damage, DNA Primase, DNA Replication, DNA-Directed DNA Polymerase, Genome, History, 20th Century, Models, Genetic, Stress, Physiological
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 25 Aug 2021 07:34
Last Modified: 25 Aug 2021 07:45
URI: http://sro.sussex.ac.uk/id/eprint/101284

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