Banca de QUALIFICAÇÃO: AIAN DOS SANTOS VIANA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : AIAN DOS SANTOS VIANA
DATE: 04/09/2026
TIME: 14:30
LOCAL: Videoconferência
TITLE:

Comparative analysis of csb-1 and xpc-1 deficiencies associated with neurological and neurodegenerative phenotypes in Caenorhabditis elegans

KEY WORDS:

csb-1; xpc-1; neurodegeneration; C. elegans, NER.

PAGES: 60
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Genomic instability is one of the main factors associated with aging and neurodegeneration and is continuously counteracted by DNA repair mechanisms, among which nucleotide excision repair (NER) plays a central role in removing bulky lesions that distort the DNA double helix. NER is organized into two subpathways—the global genome repair (GG-NER) and transcription-coupled repair (TC-NER)—whose deficiencies are associated with genetic syndromes characterized by premature aging and progressive neurodegeneration, such as Xeroderma Pigmentosum and Cockayne syndrome. This study aimed to compare the neurodegenerative impact of deficiencies in the csb-1, xpa-1, and xpc-1 genes, which are orthologous to components of TC-NER, a step common to both subpathways, and GG-NER, respectively, using the nematode Caenorhabditis elegans as an experimental model. For this purpose, deletion mutants and animals subjected to RNAi targeting the three genes were used to assess neuronal integrity by pan-neuronal fluorescence (MAH677 strain), the neuromuscular phenotype by pharyngeal pumping and body curvature, intestinal mitochondrial density (SJ4143 strain), and the chemotactic response to isoamyl alcohol (CL2355 strain). The results demonstrated a significant increase in whole-body fluorescence and a reduction in fluorescence in the head region of xpa-1-deficient animals, accompanied by increased pharyngeal pumping in xpa-1 and xpc-1 animals, with no changes in body curvature or intestinal mitochondrial density during the first 48 hours. All groups exhibited impaired chemotaxis, with the effect being more pronounced in xpa-1-deficient animals, which displayed attraction rather than the expected aversive response. It is concluded that global NER deficiency, represented by xpa-1, has a broader impact on the neuronal and neuromotor phenotypes assessed during the early stages of development, whereas isolated deficiencies in GG-NER and TC-NER, represented by xpc-1 and csb-1, respectively, produce more subtle and specific alterations, suggesting distinct contributions of each subpathway to the maintenance of neuronal homeostasis.

COMMITTEE MEMBERS:
Externo à Instituição - EVANDRO ARAUJO DE SOUZA - USP
Interna - 1837354 - JULLIANE TAMARA ARAUJO DE MELO CAMPOS
Presidente - 1453487 - KATIA CASTANHO SCORTECCI