International Journal of Molecular Sciences Review Functional Coupling between DNA Replication and Sister Chromatid Cohesion Establishment Ana Boavida 1 , Diana Santos 1 , Mohammad Mahtab 1,2 and Francesca M. Pisani 1,* 1 Istituto di Biochimica e Biologia Cellulare, Consiglio Nazionale delle Ricerche, Via P. Castellino 111, 80131 Naples, Italy;
[email protected] (A.B.);
[email protected] (D.S.);
[email protected] (M.M.) 2 Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche, Università degli Studi della Campania Luigi Vanvitelli, Via Vivaldi 43, 81100 Caserta, Italy * Correspondence:
[email protected]; Tel.: +39-0816132292 Abstract: Several lines of evidence suggest the existence in the eukaryotic cells of a tight, yet largely unexplored, connection between DNA replication and sister chromatid cohesion. Tethering of newly duplicated chromatids is mediated by cohesin, an evolutionarily conserved hetero-tetrameric protein complex that has a ring-like structure and is believed to encircle DNA. Cohesin is loaded onto chromatin in telophase/G1 and converted into a cohesive state during the subsequent S phase, a process known as cohesion establishment. Many studies have revealed that down-regulation of a number of DNA replication factors gives rise to chromosomal cohesion defects, suggesting that they play critical roles in cohesion establishment. Conversely, loss of cohesin subunits (and/or regulators) has been found to alter DNA replication fork dynamics. A critical step of the cohesion establishment process consists in cohesin acetylation, a modification accomplished by dedicated acetyltransferases that operate at the replication forks. Defects in cohesion establishment give rise to chromosome mis-segregation and aneuploidy, phenotypes frequently observed in pre-cancerous and cancerous Citation: Boavida, A.; Santos, D.; Mahtab, M.; Pisani, F.M.