title: Regulation of oxidized base damage repair by chromatin assembly factor 1 subunit A.
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.
authors: Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA cyang@houstonmethodist.org.
authors: Chunying
authors: C
authors: Yang
authors: Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA sxsengupta@houstonmethodist.org.|Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
authors: Shiladitya
authors: S
authors: Sengupta
authors: Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors: Pavana M
authors: PM
authors: Hegde
authors: Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors: Joy
authors: J
authors: Mitra
authors: Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors: Shuai
authors: S
authors: Jiang
authors: Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors: Brooke
authors: B
authors: Holey
authors: Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors: Altaf H
authors: AH
authors: Sarker
authors: Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors: Miaw-Sheue
authors: MS
authors: Tsai
authors: Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA.|Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.|Houston Methodist Neurological Institute, Houston, TX 77030, USA.
authors: Muralidhar L
authors: ML
authors: Hegde
authors: Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA smitra2@houstonmethodist.org.|Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
authors: Sankar
authors: S
authors: Mitra
mesh_terms: D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D056504:Chromatin Assembly Factor-1 / Q000378:metabolism*; D004249:DNA Damage / Q000528:radiation effects; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair; D005949:Glucose Oxidase / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D046912:Multiprotein Complexes; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011485:Protein Binding; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species; D014157:Transcription Factors
chemical_list: C489780:CNOT8 protein, human; D002843:Chromatin; D056504:Chromatin Assembly Factor-1; D006657:Histones; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D005949:Glucose Oxidase; D045647:DNA Glycosylases; C473634:NEIL1 protein, human