PARP inhibition impedes the maturation of nascent DNA strands during DNA replication

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F22%3A00565988" target="_blank" >RIV/61388971:_____/22:00565988 - isvavai.cz</a>
Alternative codes found
RIV/68378050:_____/22:00565988
Result on the web
<a href="https://www.nature.com/articles/s41594-022-00747-1" target="_blank" >https://www.nature.com/articles/s41594-022-00747-1</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41594-022-00747-1" target="_blank" >10.1038/s41594-022-00747-1</a>

Result language
angličtina
Original language name
PARP inhibition impedes the maturation of nascent DNA strands during DNA replication
Original language description
Biochemical and cell-based assays reveal that PARP inhibitors impede the maturation of nascent DNA strands during DNA replication, and implicate unligated Okazaki fragments and other nascent strand discontinuities in the cytotoxicity of these anti-cancer compounds. Poly(ADP-ribose) polymerase 1 (PARP1) is implicated in the detection and processing of unligated Okazaki fragments and other DNA replication intermediates, highlighting such structures as potential sources of genome breakage induced by PARP inhibition. Here, we show that PARP1 activity is greatly elevated in chicken and human S phase cells in which FEN1 nuclease is genetically deleted and is highest behind DNA replication forks. PARP inhibitor reduces the integrity of nascent DNA strands in both wild-type chicken and human cells during DNA replication, and does so in FEN1(-/-) cells to an even greater extent that can be detected as postreplicative single-strand nicks or gaps. Collectively, these data show that PARP inhibitors impede the maturation of nascent DNA strands during DNA replication, and implicate unligated Okazaki fragments and other nascent strand discontinuities in the cytotoxicity of these compounds.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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