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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Science: general issues --- Neurosciences --- neurodegenerative diseases --- movement disorders --- motor neuron disease --- non-motor symptoms ---  C9orf72 hexanucleotide repeat expansion --- neuropsychiatric disorders --- sleep disorders --- levodopa response

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This Special Issue of International Journal of Molecular Sciences (IJMS) is dedicated to the mechanisms mediated at the molecular and cellular levels in response to adverse genomic perturbations and DNA replication stress. The relevant proteins and processes play paramount roles in nucleic acid transactions to maintain genomic stability and cellular homeostasis. A total of 18 articles are presented which encompass a broad range of highly relevant topics in genome biology. These include replication fork dynamics, DNA repair processes, DNA damage signaling and cell cycle control, cancer biology, epigenetics, cellular senescence, neurodegeneration, and aging. As Guest Editor for this IJMS Special Issue, I am very pleased to offer this collection of riveting articles centered on the theme of DNA replication stress. The blend of articles builds upon a theme that DNA damage has profound consequences for genomic stability and cellular homeostasis that affect tissue function, disease, cancer, and aging at multiple levels and through unique mechanisms. I thank the authors for their excellent contributions, which provide new insight into this fascinating and highly relevant area of genome biology.

Werner Syndrome --- n/a --- A549 cells --- epigenetic --- neurodegeneration --- Genome integrity --- adaptation --- cellular senescence --- genome instability --- Werner Syndrome Protein --- lipofuscin --- cell cycle checkpoints --- exonuclease 1 --- template-switching --- energy metabolism --- mutation frequency --- DNA replication --- fork regression --- motor neuron disease --- Microsatellites --- Alzheimer’s disease --- chromatin remodeler --- repair of DNA damage --- AP site analogue --- mutagens --- replication timing --- Thermococcus eurythermalis --- nucleolar stress --- gene expression --- mutations spectra --- origin firing --- Fanconi Anemia --- superfamily 2 ATPase --- DNA translocation --- DNA repair --- SSB signaling --- homologous recombination --- common fragile sites --- 8-chloro-adenosine --- replication --- genome stability --- mutagenicity --- fork reversal --- multiple sclerosis --- non-B DNA --- protein stability --- heterogeneity --- ubiquitin --- SenTraGorTM (GL13) --- replication restart --- EdU --- ?-arrestin --- NER --- aging --- SSB end resection --- oxidative stress --- ATR --- dormant origins --- R loops --- DNA damage response --- Difficult-to-Replicate Sequences --- DNA double-strand repair --- endonuclease IV --- ALS --- double strand break repair --- premature aging --- replication stress --- EXO1 --- POL? --- translesion synthesis --- strand displacements --- G2-arrest --- DNA replication pattern --- SSB repair --- genome integrity --- G protein-coupled receptor kinase interacting protein 2 (GIT2) --- MMR --- replicative stress --- senolytics --- spacer --- interactome --- ATR-Chk1 DDR pathway --- C9orf72 --- replication fork restart --- translesion DNA synthesis --- DNA damage --- mismatch repair --- DNA replication stress --- DNA helicase --- Polymerase kappa --- DNA fiber assay --- H1299 cells --- TLS --- APE2 --- ageing --- cell death --- chromosome --- TopBP1 --- barley --- clock proteins --- post-translational modification --- 8-oxoG --- S phase --- ataxia telangiectasia mutated (ATM) --- G protein-coupled receptor (GPCR) --- Polymerase eta --- cancer --- G protein-coupled receptor kinase (GRK) --- helicase --- genomic instability --- Parkinson’s disease --- nucleotide excision repair --- SupF --- Alzheimer's disease --- Parkinson's disease