Model of abasic site DNA cross-link repair, from the architecture of NEIL3 DNA binding domains to the X-structure model

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00561949" target="_blank" >RIV/61388963:_____/22:00561949 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/22:10451255

Výsledek na webu

<a href="https://doi.org/10.1093/nar/gkac793" target="_blank" >https://doi.org/10.1093/nar/gkac793</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/nar/gkac793" target="_blank" >10.1093/nar/gkac793</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Model of abasic site DNA cross-link repair, from the architecture of NEIL3 DNA binding domains to the X-structure model

Popis výsledku v původním jazyce

Covalent DNA interstrand crosslinks are toxic DNA damage lesions that block the replication machinery that can cause a genomic instability. Ubiquitous abasic DNA sites are particularly susceptible to spontaneous cross-linking with a base from the opposite DNA strand. Detection of a crosslink induces the DNA helicase ubiquitination that recruits NEIL3, a DNA glycosylase responsible for the lesion removal. NEIL3 utilizes several zinc finger domains indispensable for its catalytic NEI domain repairing activity. They recruit NEIL3 to the repair site and bind the single-stranded DNA. However, the molecular mechanism underlying their roles in the repair process is unknown. Here, we report the structure of the tandem zinc-finger GRF domain of NEIL3 and reveal the molecular details of its interaction with DNA. Our biochemical data indicate the preferential binding of the GRF domain to the replication fork. In addition, we obtained a structure for the catalytic NEI domain in complex with the DNA reaction intermediate that allowed us to construct and validate a model for the interplay between the NEI and GRF domains in the recognition of an interstrand cross-link. Our results suggest a mechanism for recognition of the DNA replication X-structure by NEIL3, a key step in the interstrand cross-link repair.

Název v anglickém jazyce

Model of abasic site DNA cross-link repair, from the architecture of NEIL3 DNA binding domains to the X-structure model

Popis výsledku anglicky

Covalent DNA interstrand crosslinks are toxic DNA damage lesions that block the replication machinery that can cause a genomic instability. Ubiquitous abasic DNA sites are particularly susceptible to spontaneous cross-linking with a base from the opposite DNA strand. Detection of a crosslink induces the DNA helicase ubiquitination that recruits NEIL3, a DNA glycosylase responsible for the lesion removal. NEIL3 utilizes several zinc finger domains indispensable for its catalytic NEI domain repairing activity. They recruit NEIL3 to the repair site and bind the single-stranded DNA. However, the molecular mechanism underlying their roles in the repair process is unknown. Here, we report the structure of the tandem zinc-finger GRF domain of NEIL3 and reveal the molecular details of its interaction with DNA. Our biochemical data indicate the preferential binding of the GRF domain to the replication fork. In addition, we obtained a structure for the catalytic NEI domain in complex with the DNA reaction intermediate that allowed us to construct and validate a model for the interplay between the NEI and GRF domains in the recognition of an interstrand cross-link. Our results suggest a mechanism for recognition of the DNA replication X-structure by NEIL3, a key step in the interstrand cross-link repair.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/EF16_019%2F0000729" target="_blank" >EF16_019/0000729: Chemická biologie pro vývoj nových terapií</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nucleic Acids Research

ISSN

0305-1048

e-ISSN

1362-4962

Svazek periodika

50

Číslo periodika v rámci svazku

18

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

10436-10448

Kód UT WoS článku

000859179700001

EID výsledku v databázi Scopus

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