Base Excision Repair (BER) is a conserved, intracellular DNA repair system that recognizes and removes chemically modified bases to insure genomic integrity and prevent mutagenesis. Aberrant BER has been tightly linked with a broad spectrum of human pathologies, such as several types of cancer, neurological degeneration, developmental abnormalities, immune dysfunction and aging. In the cell, BER must recognize and remove DNA lesions from the tightly condensed, protein-coated chromatin. Because chromatin is necessarily refractory to DNA metabolic processes, like transcription and replication, the compaction of the genomic material is also inhibitory to the repair systems necessary for its upkeep. Multiple ATP-dependent chromatin remodelling (ACR) complexes play essential roles in modulating the protein-DNA interactions within chromatin, regulating transcription and promoting activities of some DNA repair systems, including double-strand break repair and nucleotide excision repair. However, it remains unclear how BER operates in the context of chromatin, and if the chromatin remodelling processes that govern transcription and replication also actively regulate the efficiency of BER. In this review we highlight the emerging role of ACR in regulation of BER.
Bibliographical noteFunding Information:
The authors would like to thank Mick Smerdon for his insight and direction during their time in the DNA Repair Shop at Washington State University. In addition, Antonio Conconi deserves a tremendous amount of gratitude for all of his efforts in assembling this special addition of DNA Repair. Work for this review was funded in part by grants ES002095 (to JMH ) and ES004106 and ES002614 (to M. Smerdon) from the National Institute of Environmental Health Sciences (NIEHS) . Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS or NIH.
© 2015 Elsevier B.V.
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- AP endonuclease
- Chromatin remodeling
- DNA damage
- Polymerase β