Pathology of DNA Replication
Genetic instability is a major feature of tumor cells and is associated with the process of carcinogenesis in humans. In many cases, such instability occurs during the S phase and is due to DNA replication defects. The enzymatic machinery of replication used to copy and reproduce the DNA is called “replisome”. Replisome progression is subject to numerous control systems because its disruption can produce changes in the genome. DNA replication may be hampered by barriers that slow, temporarily stop or block the progression of replicative DNA polymerases. These obstacles may have different causes: a) secondary structures in DNA, b) complex DNA-protein, c) changes in chromatin and d) DNA damage. If the arrested replication forks are not appropriately processed , chromosomal rearrangements (translocations, inversions or deletions) may occur and contribute to early stages of carcinogenesis. In this context, we study the functions of translesional DNA polymerases that may contribute to bypass break sites. Actually, we think that it is important to understand these aspects of DNA replication, both in terms of mechanisms of emergence of such obstacles and their functional consequences.
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