Roles for the 3D genome in the cell cycle, DNA replication, and double strand break repair

Katherine A Giles ^1,2* Phillippa C Taberlay ² Anthony J Cesare ¹ Mathew JK Jones ^3,4*

• ¹ University of Sydney, Children's Medical Research Institute, Sydney, Australia
• ² Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, Tasmania, Australia
• ³ Frazer Institute The University of Queensland, Brisbane, Australia
• ⁴ School of Chemistry and Molecular Biosciences, Faculty of Science, The University of Queensland, Brisbane, Queensland, Australia

Large eukaryotic genomes are packaged into the restricted area of the nucleus to protect the genetic code and provide a dedicated environment to read, copy and repair DNA. The physical organisation of the genome into chromatin loops and self-interacting domains provides the basic structural units of genome architecture. These structural arrangements are complex, multi-layered, and highly dynamic and influence how different regions of the genome interact. The role of chromatin structures during transcription via enhancer-promoter interactions is well established. Less understood is how nuclear architecture influences the plethora of chromatin transactions during DNA replication and repair. In this review, we discuss how genome architecture is regulated during the cell cycle to influence the positioning of replication origins and the coordination of DNA double strand break repair. The role of genome architecture in these cellular processes highlights its critical involvement in preserving genome integrity and cancer prevention.