DNA replication stress: from molecular mechanisms to human disease
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The genome of proliferating cells must be precisely duplicated in each cell division cycle. Chromosomal replication entails risks such as the possibility of introducing breaks and/or mutations in the genome. Hence, DNA replication requires the coordinated action of multiple proteins and regulatory factors, whose deregulation causes severe developmental diseases and predisposes to cancer. In recent years, the concept of “replicative stress” (RS) has attracted much attention as it impinges directly on genomic stability and offers a promising new avenue to design anticancer therapies. In this review, we summarize recent progress in three areas: (1) endogenous and exogenous factors that contribute to RS, (2) molecular mechanisms that mediate the cellular responses to RS, and (3) the large list of diseases that are directly or indirectly linked to RS.
KeywordsDNA replication Replicative stress Replication fork Replication origin Checkpoint DNA repair
We thank all members of the laboratory for useful discussions and apologize to the authors whose works are not cited due to space restrictions.
Compliance with ethical standards
This review article does not contain any studies with human participants or animals performed by any of the authors.
Conflict of interest
The authors declare that they have no competing interests.
Research in JM lab is supported by grants BFU2013-49153P and Consolider CSD2007-00015 from the Spanish Ministry of Economy and Competitiveness.
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