Faithful transmission and maintenance of the integrity of genetic information in the cell is controlled by a set of coordinated processes that involve chromatin remodeling, cell cycle checkpoint control, DNA replication, recombination and repair. A defect in any of these tightly regulated processes would result in gross chromosomal rearrangements, such as chromosome deletion, insertion, duplication, translocation and loss and lead to tumorigenesis or cell death. In eukaryotic cells, DNA is packaged into a highly compacted inaccessible structure called the chromatin by both histones and nonhistone proteins., Cells rely on post-translational histone modifications and ATP-dependent chromatin remodeling machines to gain access to, and perform various functions on, DNA. Histones can be reversibly modified in several ways, including methylation, ubiquitylation, acetylation and phosphorylation. Histone acetylation is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HATs are a diverse set of enzymes that are evolutionarily conserved from yeast to humans and are usually subunits of large co-activator complexes, namely the humanTBP-free TAF complex (TFTC), SPT3/TAF9/GCN5 complex (STAGA) (human homolog of yeast SAGA complex) and the activation 2a (Ada2a)-containing (ATAC) complex. These co-activator complexes function in many cellular processes, including transcription, cell cycle progression and DNA replication and repair.,HumanAda3 is an essential component of the ATAC complex, which is composed of ADA2, ADA3 and GCN5. Ada3 protein associates with and regulates transcriptional activity of estrogen receptor and retinoic acid receptor. Ada3 also binds and stabilizes the tumor suppressor p53 and is required for p53 acetylation by p300. Although several cellular functions of Ada3 as part of multiple HAT complexes have been identified, the in vivo physiological roles of mammalianAda3 were unclear, until a recent study by the Band Laboratory that demonstrated an essential role of mammalianAda3 in embryonic development as well as cell cycle progression. In a recent issue of Cell Cycle, Mirza et al. discovered another interesting function of Ada3: it participates in DNA repair and in the maintenance of genomic stability. Using adenovirus-Cre-mediated Ada3 deletion in Ada3mouse embryonic fibroblasts, Mirza et al. showed that Ada3 depletion is accompanied by increased levels of pATM, γH2AX, p53BP1 and pRAD51, even before ionizing radiation, indicating that Ada3 deficiency results in increased DNA damage in the cell. Ada3 does not appear to be required for DNA damage sensing or checkpoint activation; however, a delay in DNA repair was observed in Ada3−/− cells.The authors further asked whether Ada3 deletion would affect chromosomal stability. They found that chromosome condensation was normal in Ada3−/− cells, whereas increased chromosome aberrations, ranging from chromosome breaks, fragments, deletions and translocations, were observed in these cells, suggesting that Ada3 plays an important role in maintaining genome integrity. Interestingly, the frequency of chromosomal aberrations in Ada3-deleted S-phase cells upon DNA damage was significantly higher than that in control or Ada3-deleted G1- or G2-phase cells. The authors also observed delayed disappearance of CtIP foci after DNA damage in Ada3−/− cells. Since CtIP is known to act in both cell cycle checkpoint and DNA repair,, this delay in the disappearance of CtIP foci may explain both the checkpoint defects and DNA repair deficiency observed in Ada3−/− cells.The findings of Mirza et al. not only establish a novel function of Ada3 in DNA repair and genome maintenance, but also open up a new direction for the studies of HAT complexes in DNA damage response. It would be interesting to further decipher the precise molecular mechanism underlying the functions of Ada3 and its associated HAT complexes in cell cycle checkpoint control, DNA repair and the maintenance of genome stability.