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Nucleic Acids Res. 2017 Jan 25;45(2):739-748. doi: 10.1093/nar/gkw1024. Epub 2016 Oct 27.

Regulation of oxidized base damage repair by chromatin assembly factor 1 subunit A.

Author information

1
Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA cyang@houstonmethodist.org.
2
Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA sxsengupta@houstonmethodist.org.
3
Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
4
Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA.
5
Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
6
Houston Methodist Neurological Institute, Houston, TX 77030, USA.
7
Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA smitra2@houstonmethodist.org.

Abstract

Reactive oxygen species (ROS), generated both endogenously and in response to exogenous stress, induce point mutations by mis-replication of oxidized bases and other lesions in the genome. Repair of these lesions via base excision repair (BER) pathway maintains genomic fidelity. Regulation of the BER pathway for mutagenic oxidized bases, initiated by NEIL1 and other DNA glycosylases at the chromatin level remains unexplored. Whether single nucleotide (SN)-BER of a damaged base requires histone deposition or nucleosome remodeling is unknown, unlike nucleosome reassembly which is shown to be required for other DNA repair processes. Here we show that chromatin assembly factor (CAF)-1 subunit A (CHAF1A), the p150 subunit of the histone H3/H4 chaperone, and its partner anti-silencing function protein 1A (ASF1A), which we identified in human NEIL1 immunoprecipitation complex, transiently dissociate from chromatin bound NEIL1 complex in G1 cells after induction of oxidative base damage. CHAF1A inhibits NEIL1 initiated repair in vitro Subsequent restoration of the chaperone-BER complex in cell, presumably after completion of repair, suggests that histone chaperones sequester the repair complex for oxidized bases in non-replicating chromatin, and allow repair when oxidized bases are induced in the genome.

PMID:
27794043
PMCID:
PMC5314755
DOI:
10.1093/nar/gkw1024
[Indexed for MEDLINE]
Free PMC Article

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