Ataxia-telangiectasia (A-T), an autosomal recessive disorder, occurs In a ratio of 1:40,000- 1:100,000 live births, with the primary feature of progressive gait and truncal ataxia. It is a progressive, degenerative disease characterized by cerebellar degeneration, and also by immunodeficiency, radiosensitivity and a predisposition to cancer. The pleiotropic nature of the disease is now explained by the function of the protein, which in its mutated form causes A-T. This protein, ataxia-telangiectasia mutated (ATM) has been shown to be a protein kinase and is vital in orchestrating DNA damage repair, cell cycle checkpoint control and is likely to also play a role in hitherto undefined functions in the cytoplasm of neurons. Further, the ATM protein is activated in response to ionising radiation (IR), a key factor in the formation of DNA double strand breaks. Also, current knowledge positions ATM as a signal transducer of such DNA damage rather than as its sensor. The substrates of the ATM protein have been a subject of intense study and investigations have revealed numerous targets such as p53, Nbs1 and Chk2 to name only a few. Two proteins related to ATM by virtue of their homology to ATM’s C-terminus catalytic PI3K domain, are ATR and DNA-PK, all three collectively termed PI3K-like- kinases (PIKK). Modes of activation for each of these three proteins are different. However, they show some redundancy in their specificity for substrates involved in the cell cycle checkpoint and DNA damage repair pathways. It was shown that ATM along with a gamut of other proteins involved in DNA damage recognition and repair form a large dynamic complex, which was termed the Brcal-associated-surveillance complex (BASC). ATR and DNA-PK too have been shown to occur in large protein complexes. Thus, it is emerging that studies of protein complexes will help better understand the signal transduction pathways that initiate and mediate DNA damage recognition and repair whilst activating the cell cycle checkpoint mechanism. It was the purpose of this study to assess the size-distribution of ATM, and in relation to this, investigate the size-distribution of various proteins such as DNA-PK, ATR, Chk1 and Nbs1. It was also the aim to study the well-documented enzymatic activity of ATM, albeit from high molecular weight fractions. Further, as part of determining the localisation of proteins, the chromatin association of proteins and protein-complexes was determined. All of the above stated aims will facilitate in furthering our understanding on how ATM interacts with other cellular components and also will also facilitate in understanding its activity in response to DNA double strand breaks. It has been shown in this study that ATM and ATR occur in high molecular weight regions and based on previous studies (Wang et al. 2000), these findings corroborate the idea that ATM and ATR are part of the BASC, or in other high molecular weight complexes. DNA-PK too is seen in high molecular weight fractions and raises the possibility that it could be part of the BASC or other complexes. In relation to the interacting partners of ATM, the story is somewhat different, with some proteins occurring in high molecular weight fractions before IR and others after IR. As part of studying ATM protein complexes, the kinase activity of ATM in high molecular weight fractions was also assessed. While it was shown in our study that IR activates ATM kinase activity, stimulates ATM autophosphorylation and in conjunction with ATP further augments the enzymatic activity of ATM, it was not possible to show conclusively such kinase activity in protein complexes that contained ATM. Since it was shown in this study that ATM was simultaneously occurring in a range of high molecular weight fractions and as a monomer, it was hypothesised that ATM was involved in various cellular activities at any one given moment in time. One such activity is that ATM, like its other PIKK family member DNA-PK, may be associating with chromatin. The findings in this study corroborate previous studies and show ATM binds to chromatin. With regards to interacting partners of ATM and, a member of the PIKK family - DNA-PK, however, the responses are varied. For example, in the absence of ATM there is increased binding of DNA-PK onto chromatin. Also, our studies have shown that two of the components of the MRN complex, namely Mre11 and Nbs1 bind to chromatin independently of ATM. Further study of ATM protein complexes is warranted as this will aid in understanding the signal transduction pathways that are involved in DNA damage recognition, transduction and repair. Also clarification of the exact mechanism of activation of ATM is crucial to developing a clear understanding of the ATM protein.