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Review
. 2018 Apr;75(8):1325-1338.
doi: 10.1007/s00018-017-2717-4. Epub 2017 Nov 23.

CREBBP and p300 lysine acetyl transferases in the DNA damage response

Ilaria Dutto  1   2 , Claudia Scalera  1 , Ennio Prosperi  3
Affiliations
Review

CREBBP and p300 lysine acetyl transferases in the DNA damage response

Ilaria Dutto et al. Cell Mol Life Sci. 2018 Apr.

Abstract

The CREB-binding protein (CREBBP, or in short CBP) and p300 are lysine (K) acetyl transferases (KAT) belonging to the KAT3 family of proteins known to modify histones, as well as non-histone proteins, thereby regulating chromatin accessibility and transcription. Previous studies have indicated a tumor suppressor function for these enzymes. Recently, they have been found to acetylate key factors involved in DNA replication, and in different DNA repair processes, such as base excision repair, nucleotide excision repair, and non-homologous end joining. The growing list of CBP/p300 substrates now includes factors involved in DNA damage signaling, and in other pathways of the DNA damage response (DDR). This review will focus on the role of CBP and p300 in the acetylation of DDR proteins, and will discuss how this post-translational modification influences their functions at different levels, including catalytic activity, DNA binding, nuclear localization, and protein turnover. In addition, we will exemplify how these functions may be necessary to efficiently coordinate the spatio-temporal response to DNA damage. CBP and p300 may contribute to genome stability by fine-tuning the functions of DNA damage signaling and DNA repair factors, thereby expanding their role as tumor suppressors.

Keywords: DNA repair; DNA repair enzymes; DNA replication; Post-translational modification; Protein acetylation.

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Figures

Fig. 1
Fig. 1
Schematic representation of p300 and CBP proteins. The cysteine/histidine (CH) rich regions 1 and 3 are shown, while the CH2 region (not indicated) contains both the bromodomain (BrD) and RING (R) domains. Also shown is the region containing the lysine acetyl transferase (KAT) catalytic activity. Numbers indicate the length of each protein. Colored bars shown below represent the regions involved in the interaction with the indicated DDR factors. For comparison, the regions responsible for p53 binding are also shown
Fig. 2
Fig. 2
Schematic representation of protein substrates of p300 and CBP participating in different aspects of the DNA damage response. Each block represents a group of proteins involved in the same process (e.g., DNA replication/repair, DNA damage signaling, NER, BER, etc.)
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