TY - JOUR
T1 - Nucleases Acting at Stalled Forks
T2 - How to Reboot the Replication Program with a Few Shortcuts
AU - Pasero, Philippe
AU - Vindigni, Alessandro
N1 - Funding Information:
We thank K. Cimprich, A. Constantinou, and S. Lambert for their careful reading of the manuscript and insightful comments. The work in the laboratory of P.P. is supported by l’Agence Nationale de la Recherche, l’Institut National du Cancer, and la Ligue Nationale Contre le Cancer (Equipe Labellisée), as well as by the Merck Sharpe & Dohme Avenir Fund. The work in the A.V. laboratory is supported by National Institutes of Health grant R01GM108648 and by Department of Defense Breast Cancer Research Program Breakthrough Award BC151728.
Publisher Copyright:
Copyright © 2017 by Annual Reviews. All rights reserved.
PY - 2017/11/27
Y1 - 2017/11/27
N2 - In a lifetime, a human being synthesizes approximately 2×1016 meters of DNA, a distance that corresponds to 130,000 times the distance between the Earth and the Sun. This daunting task is executed by thousands of replication forks, which progress along the chromosomes and frequently stall when they encounter DNA lesions, unusual DNA structures, RNA polymerases, or tightly-bound protein complexes. To complete DNA synthesis before the onset of mitosis, eukaryotic cells have evolved complex mechanisms to process and restart arrested forks through the coordinated action of multiple nucleases, topoisomerases, and helicases. In this review, we discuss recent advances in understanding the role and regulation of nucleases acting at stalled forks with a focus on the nucleolytic degradation of nascent DNA, a process commonly referred to as fork resection. We also discuss the effects of deregulated fork resection on genomic instability and on the unscheduled activation of the interferon response under replication stress conditions.
AB - In a lifetime, a human being synthesizes approximately 2×1016 meters of DNA, a distance that corresponds to 130,000 times the distance between the Earth and the Sun. This daunting task is executed by thousands of replication forks, which progress along the chromosomes and frequently stall when they encounter DNA lesions, unusual DNA structures, RNA polymerases, or tightly-bound protein complexes. To complete DNA synthesis before the onset of mitosis, eukaryotic cells have evolved complex mechanisms to process and restart arrested forks through the coordinated action of multiple nucleases, topoisomerases, and helicases. In this review, we discuss recent advances in understanding the role and regulation of nucleases acting at stalled forks with a focus on the nucleolytic degradation of nascent DNA, a process commonly referred to as fork resection. We also discuss the effects of deregulated fork resection on genomic instability and on the unscheduled activation of the interferon response under replication stress conditions.
KW - Exonucleases
KW - Genomic instability
KW - Homologous recombination
KW - Replication forks
KW - Replication stress
KW - Structure-specific nucleases
UR - http://www.scopus.com/inward/record.url?scp=85036514120&partnerID=8YFLogxK
U2 - 10.1146/annurev-genet-120116-024745
DO - 10.1146/annurev-genet-120116-024745
M3 - Review article
C2 - 29178820
AN - SCOPUS:85036514120
VL - 51
SP - 477
EP - 499
JO - Annual Review of Genetics
JF - Annual Review of Genetics
SN - 0066-4197
ER -