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Zinc finger protein ZNF384 is an adaptor of Ku to DNA during classical non-homologous end-joining
- Source :
- Nature Communications, Nature Communications, 2021, 12 (1), pp.6560. ⟨10.1038/s41467-021-26691-0⟩, Nature Communications, Nature Publishing Group, 2021, 12 (1), pp.6560. ⟨10.1038/s41467-021-26691-0⟩, Nature Communications, 12(1). NATURE PORTFOLIO, Nature Communications, Vol 12, Iss 1, Pp 1-21 (2021), Nature communications, 12(1):6560. Nature Publishing Group
- Publication Year :
- 2021
-
Abstract
- DNA double-strand breaks (DSBs) are among the most deleterious types of DNA damage as they can lead to mutations and chromosomal rearrangements, which underlie cancer development. Classical non-homologous end-joining (cNHEJ) is the dominant pathway for DSB repair in human cells, involving the DNA-binding proteins XRCC6 (Ku70) and XRCC5 (Ku80). Other DNA-binding proteins such as Zinc Finger (ZnF) domain-containing proteins have also been implicated in DNA repair, but their role in cNHEJ remained elusive. Here we show that ZNF384, a member of the C2H2 family of ZnF proteins, binds DNA ends in vitro and is recruited to DSBs in vivo. ZNF384 recruitment requires the poly(ADP-ribosyl) polymerase 1 (PARP1)-dependent expansion of damaged chromatin, followed by binding of its C2H2 motifs to the exposed DNA. Moreover, ZNF384 interacts with Ku70/Ku80 via its N-terminus, thereby promoting Ku70/Ku80 assembly and the accrual of downstream cNHEJ factors, including APLF and XRCC4/LIG4, for efficient repair at DSBs. Altogether, our data suggest that ZNF384 acts as a ‘Ku-adaptor’ that binds damaged DNA and Ku70/Ku80 to facilitate the build-up of a cNHEJ repairosome, highlighting a role for ZNF384 in DSB repair and genome maintenance.<br />Classical non-homologous end-joining (cNHEJ) is the dominant pathway used by human cells to repair DNA double-strand breaks (DSBs) and maintain genome stability. Here the authors show that PARP1-driven chromatin expansion allows the recruitment of ZNF384, which in turn recruits Ku70/Ku80 to facilitate cNHEJ.
- Subjects :
- Ku80
DNA damage
DNA repair
Science
[SDV]Life Sciences [q-bio]
General Physics and Astronomy
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
DNA-binding proteins
Humans
DNA Breaks, Double-Stranded
Non-homologous-end joining
030304 developmental biology
Zinc finger
0303 health sciences
Ku70
Multidisciplinary
Chemistry
fungi
DNA
General Chemistry
DNA repair protein XRCC4
Chromatin
Cell biology
Non-homologous end joining
[SDV] Life Sciences [q-bio]
030220 oncology & carcinogenesis
Trans-Activators
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications, Nature Communications, 2021, 12 (1), pp.6560. ⟨10.1038/s41467-021-26691-0⟩, Nature Communications, Nature Publishing Group, 2021, 12 (1), pp.6560. ⟨10.1038/s41467-021-26691-0⟩, Nature Communications, 12(1). NATURE PORTFOLIO, Nature Communications, Vol 12, Iss 1, Pp 1-21 (2021), Nature communications, 12(1):6560. Nature Publishing Group
- Accession number :
- edsair.doi.dedup.....d300eba28f4d2643c3344084226732c5