DNA replication origins—where do we begin?

Author:

Prioleau Marie-Noëlle,MacAlpine David M.

Abstract

For more than three decades, investigators have sought to identify the precise locations where DNA replication initiates in mammalian genomes. The development of molecular and biochemical approaches to identify start sites of DNA replication (origins) based on the presence of defining and characteristic replication intermediates at specific loci led to the identification of only a handful of mammalian replication origins. The limited number of identified origins prevented a comprehensive and exhaustive search for conserved genomic features that were capable of specifying origins of DNA replication. More recently, the adaptation of origin-mapping assays to genome-wide approaches has led to the identification of tens of thousands of replication origins throughout mammalian genomes, providing an unprecedented opportunity to identify both genetic and epigenetic features that define and regulate their distribution and utilization. Here we summarize recent advances in our understanding of how primary sequence, chromatin environment, and nuclear architecture contribute to the dynamic selection and activation of replication origins across diverse cell types and developmental stages.

Funder

National Institutes of Health

American Cancer Society

Association pour la Recherche sur le Cancer

Agence Nationale pour la Recherche

IdEx Paris Sorbonne

Institut National de la Santé et de la Recherche Médicale

Publisher

Cold Spring Harbor Laboratory

Subject

Developmental Biology,Genetics

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