The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
The Importance of Poly(ADP-Ribose) Polymerase as a Sensor of Unligated Okazaki Fragments during DNA Replication
Open accessAbstract
Poly(ADP-ribose) is synthesized by PARP enzymes during the repair of stochastic DNA breaks. Surprisingly, however, we show that most if not all endogenous poly(ADP-ribose) is detected in normal S phase cells at sites of DNA replication. This S phase poly(ADP-ribose) does not result from damaged or misincorporated nucleotides or from DNA replication stress. Rather, perturbation of the DNA replication proteins LIG1 or FEN1 increases S phase poly(ADP-ribose) more than 10-fold, implicating unligated Okazaki fragments as the source of S phase PARP activity. Indeed, S phase PARP activity is ablated by suppressing Okazaki fragment formation with emetine, a DNA replication inhibitor that selectively inhibits lagging strand synthesis. Importantly, PARP activation during DNA replication recruits the single-strand break repair protein XRCC1, and human cells lacking PARP activity and/or XRCC1 are hypersensitive to FEN1 perturbation. Collectively, our data indicate that PARP1 is a sensor of unligated Okazaki fragments during DNA replication and facilitates their repair.
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Cites
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Farmer, H., McCabe, N., Lord, C. J., Tutt, A. N. J., Johnson, D. A., Richardson, T. B., Santarosa, M., Dillon, K. J., Hickson, I., Knights, C., et al. (2005) · Nature · doi:10.1038/nature03445 · Cited by 6,683
Instability and decay of the primary structure of DNA
Lindahl, T. (1993) · Nature · doi:10.1038/362709a0 · Cited by 5,679
Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
Bryant, H. E., Schultz, N., Thomas, H. D., Parker, K. M., Flower, D., Lopez, E., Kyle, S., Meuth, M., Curtin, N. J., & Helleday, T. (2005) · Nature · doi:10.1038/nature03443 · Cited by 5,198
A macrodomain-containing histone rearranges chromatin upon sensing PARP1 activation
Timinszky, G., Till, S., Hassa, P. O., Hothorn, M., Kustatscher, G., Nijmeijer, B., Colombelli, J., Altmeyer, M., Stelzer, E. H. K., Scheffzek, K., et al. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1664 · Cited by 416
RNase H2-Initiated Ribonucleotide Excision Repair
Sparks, J. L., Chon, H., Cerritelli, S. M., Kunkel, T. A., Johansson, E., Crouch, R. J., & Burgers, P. M. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.06.035 · Cited by 339
XRCC1 mutation is associated with PARP1 hyperactivation and cerebellar ataxia
Care4Rare Canada Consortium, Hoch, N. C., Hanzlikova, H., Rulten, S. L., Tétreault, M., Komulainen, E., Ju, L., Hornyak, P., Zeng, Z., Gittens, W., et al. (2017) · Nature · doi:10.1038/nature20790 · Cited by 269
Self-citationLimoli, C. L., Giedzinski, E., Bonner, W. M., & Cleaver, J. E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.231611798 · Cited by 210
Rydberg, B., & Game, J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.262591699 · Cited by 191
Cited by
Targeting DNA damage response pathways in cancer
Groelly, F. J., Fawkes, M., Dagg, R. A., Blackford, A. N., & Tarsounas, M. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-022-00535-5 · Cited by 836
PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance
Rose, M., Burgess, J. T., O’Byrne, K., Richard, D. J., & Bolderson, E. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.564601 · Cited by 719
PARP and PARG inhibitors in cancer treatment
Slade, D. (2020) · Genes & Development · doi:10.1101/gad.334516.119 · Cited by 667
Murai, J., Thomas, A., Miettinen, M., & Pommier, Y. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.05.009 · Cited by 172
Marzi, L., Szabova, L., Gordon, M., Weaver Ohler, Z., Sharan, S. K., Beshiri, M. L., Etemadi, M., Murai, J., Kelly, K., & Pommier, Y. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-0419 · Cited by 60
Metadata
- Authors
- Hanzlikova, H., Kalasova, I., Demin, A. A., Pennicott, L. E., Cihlarova, Z., & Caldecott, K. W.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 71
- Issue
- 2
- Pages
- 319-331.e3
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2852866740
- Cited by
- 393
- References
- 8
- FWCI
- 10.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: The Importance of Poly(ADP-Ribose) Polymerase as a Sensor of Unligated Okazaki Fragments during DNA Replication. https://app.cochat.ai/papers/10.1016/j.molcel.2018.06.004
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- Hanzlikova, H., Kalasova, I., Demin, A. A., Pennicott, L. E., Cihlarova, Z., & Caldecott, K. W. (2018). The Importance of Poly(ADP-Ribose) Polymerase as a Sensor of Unligated Okazaki Fragments during DNA Replication. Molecular Cell. https://doi.org/10.1016/j.molcel.2018.06.004
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
