Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/ijms22062810
Keywords
DNA replication; replication proteins; sister chromatid cohesion; cohesin; cell cycle
Funding
- Regione Campania, POR-FESR 2014-2020 Progetto SATIN
- Consorzio CNCCS (Progetto B-Ricerca di nuovi farmaci per malattie rare trascurate e della poverta)
- European Union H2020 MSCA-ETN 2019, AntiHelix [859853]
- Marie Curie Actions (MSCA) [859853] Funding Source: Marie Curie Actions (MSCA)
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In eukaryotic cells, a tight connection exists between DNA replication and sister chromatid cohesion via cohesin. Cohesin is loaded onto chromatin in telophase/G1 and converted into a cohesive state during S phase. Down-regulation of DNA replication factors can lead to cohesion defects.
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 cells. Herein, we will review our present knowledge of the molecular mechanisms underlying the functional link between DNA replication and cohesion establishment, a phenomenon that is unique to the eukaryotic organisms.
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