Early recruitment of PARP-dependent m(8)A RNA methylation at DNA lesions is subsequently accompanied by active DNA demethylation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F22%3A00565104" target="_blank" >RIV/68081707:_____/22:00565104 - isvavai.cz</a>

Result on the web

<a href="https://www.tandfonline.com/doi/full/10.1080/15476286.2022.2139109" target="_blank" >https://www.tandfonline.com/doi/full/10.1080/15476286.2022.2139109</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/15476286.2022.2139109" target="_blank" >10.1080/15476286.2022.2139109</a>

Result language

angličtina

Original language name

Early recruitment of PARP-dependent m(8)A RNA methylation at DNA lesions is subsequently accompanied by active DNA demethylation

Original language description

RNA methylation, especially 6-methyladenosine (m(6)A)-modified RNAs, plays a specific role in DNA damage response (DDR). Here, we also observe that RNA modified at 8-methyladenosine (m(8)A) is recruited to UVA-damaged chromatin immediately after microirradiation. Interestingly, the level of m(8)A RNA at genomic lesions was reduced after inhibition of histone deacetylases and DNA methyltransferases. It appears in later phases of DNA damage response, accompanied by active DNA demethylation. Also, PARP inhibitor (PARPi), Olaparib, prevented adenosine methylation at microirradiated chromatin. PARPi abrogated not only m(6)A and m(8)A RNA positivity at genomic lesions, but also XRCC1, the factor of base excision repair (BER), did not recognize lesions in DNA. To this effect, Olaparib enhanced the genome-wide level of gamma H2AX. This histone modification interacted with m(8)A RNAs to a similar extent as m(8)A RNAs with DNA. Pronounced interaction properties we did not observe for m(6)A RNAs and DNA, however, m(6)A RNA interacted with XRCC1 with the highest efficiency, especially in microirradiated cells. Together, we show that the recruitment of m(6)A RNA and m(8)A RNA to DNA lesions is PARP dependent. We suggest that modified RNAs likely play a role in the BER mechanism accompanied by active DNA demethylation. In this process, gamma H2AX stabilizes m(6)A/m(8)A-positive RNA-DNA hybrid loops via its interaction with m(8)A RNAs. R-loops could represent basic three-stranded structures recognized by PARP-dependent non-canonical m(6)A/m(8)A-mediated DNA repair pathway.

Czech name

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Czech description

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Type

J_imp - 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

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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

Name of the periodical

RNA biology

ISSN

1547-6286

e-ISSN

1555-8584

Volume of the periodical

19

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

19

Pages from-to

1153-1171

UT code for WoS article

000884574000001

EID of the result in the Scopus database

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