Mitochondrial exonuclease EXOG supports DNA integrity by the removal of single-stranded DNA flaps - Publikacja - MOST Wiedzy

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Mitochondrial exonuclease EXOG supports DNA integrity by the removal of single-stranded DNA flaps

Abstrakt

Single-stranded DNA (ssDNA) is an important intermediate generated during various cellular DNA transactions, primarily during long-patch base excision repair. When displaced by DNA polymerase during strand displacement DNA synthesis, ssDNA forms 5′ overhangs (flaps) that are either cleaved by DNA nucleases or protected from degradation upon binding of single-stranded DNA-binding proteins (SSB). Several nucleases are involved in the removal of ssDNA flaps in human mitochondria, namely the endonucleases FEN1 and DNA2, as well as the exonuclease MGME1. In this study, we show that another mitochondrial nuclease, EXOG, cleaves DNA flaps in both free and SSB-protected forms. We established that the presence of the Wing domain in EXOG structure provides additional binding site for ssDNA and 5′ flaps irrespective of monovalent salt concentration. Importantly, DNA flap cleavage by EXOG is compatible with the activity of other mitochondrial enzymes involved in DNA replication/repair, e.g. mtSSB, Pol γ, and Lig III, as we were able to reconstitute a multistep reaction of DNA synthesis, flap removal, and nick ligation. Our findings highlight the versatile role of EXOG in maintaining mitochondrial DNA integrity, expanding its DNA processing repertoire to include ssDNA flap removal.

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Informacje szczegółowe

Kategoria:
Publikacja w czasopiśmie
Typ:
artykuły w czasopismach
Opublikowano w:
NUCLEIC ACIDS RESEARCH nr 53, strony 1 - 16,
ISSN: 0305-1048
Język:
angielski
Rok wydania:
2025
Opis bibliograficzny:
Karłowicz A., Dubiel A., Wyszkowska M., Hossain K. A., Czub J.: Mitochondrial exonuclease EXOG supports DNA integrity by the removal of single-stranded DNA flaps// NUCLEIC ACIDS RESEARCH -,iss. 53 (2025), s.gkaf09-
DOI:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1093/nar/gkaf099
Źródła finansowania:
  • Publikacja bezkosztowa
Weryfikacja:
Politechnika Gdańska

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