This proposal is focused on elucidating the biochemical basis of aberrant DNA synthesis in the dividing and non-dividing cells in eucaryotic organisms, with strong emphasis placed on the study of brain cells. Somatic mutations are an important source of human disease. In addition to mutations occurring in dividing cell populations, there is accumulating evidence that mutations are also occurring in non-dividing cells, both procaryotic and eucaryotic. Genomic DNA is constantly undergoing potentially deleterious modifications in the form of slippage expansions and deletions, deaminations, loss of bases, UV damage, and chemically-induced adduct formations, to cite just a few examples. All living organisms have evolved powerful, highly selective biochemical pathways to repair damaged DNA. However, these repair processes are not perfect, and indeed they cannot be, because living organisms must be able to mutate in order to adapt to changing local environments and to evolve. Our proposal addresses questions of how eucaryotic cells copy DNA containing unrepaired lesions. There is recent evidence for an alternative pathway to apoptosis (programmed cell death), involving """"""""error-prone"""""""" eucaryotic proteins required to alleviate blocked DNA synthesis at lesion sites and to catalyze lesion bypass leading to mutations.
Our specific aims re to identify, purify and characterize eucaryotic lesion bypass proteins.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
3P50AG005142-16S2
Application #
6295384
Study Section
Project Start
1999-07-01
Project End
2000-03-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
16
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Tang, Yuchun; Sun, Wei; Toga, Arthur W et al. (2018) A probabilistic atlas of human brainstem pathways based on connectome imaging data. Neuroimage 169:227-239
Kamara, Dennis M; Gangishetti, Umesh; Gearing, Marla et al. (2018) Cerebral Amyloid Angiopathy: Similarity in African-Americans and Caucasians with Alzheimer's Disease. J Alzheimers Dis 62:1815-1826
Babulal, Ganesh M; Quiroz, Yakeel T; Albensi, Benedict C et al. (2018) Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need. Alzheimers Dement :
Kaur, Antarpreet; Edland, Steven D; Peavy, Guerry M (2018) The MoCA-Memory Index Score: An Efficient Alternative to Paragraph Recall for the Detection of Amnestic Mild Cognitive Impairment. Alzheimer Dis Assoc Disord 32:120-124
Petok, Jessica R; Myers, Catherine E; Pa, Judy et al. (2018) Impairment of memory generalization in preclinical autosomal dominant Alzheimer's disease mutation carriers. Neurobiol Aging 65:149-157
Brenowitz, Willa D; Han, Fang; Kukull, Walter A et al. (2018) Treated hypothyroidism is associated with cerebrovascular disease but not Alzheimer's disease pathology in older adults. Neurobiol Aging 62:64-71
Davis, Jeremy J (2018) Performance validity in older adults: Observed versus predicted false positive rates in relation to number of tests administered. J Clin Exp Neuropsychol 40:1013-1021
Cruchaga, Carlos; Del-Aguila, Jorge L; Saef, Benjamin et al. (2018) Polygenic risk score of sporadic late-onset Alzheimer's disease reveals a shared architecture with the familial and early-onset forms. Alzheimers Dement 14:205-214
Lin, Ming; Gong, Pinghua; Yang, Tao et al. (2018) Big Data Analytical Approaches to the NACC Dataset: Aiding Preclinical Trial Enrichment. Alzheimer Dis Assoc Disord 32:18-27
Gallagher, Damien; Kiss, Alex; Lanctot, Krista L et al. (2018) Toward Prevention of Mild Cognitive Impairment in Older Adults With Depression: An Observational Study of Potentially Modifiable Risk Factors. J Clin Psychiatry 80:

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