Apicomplexan parasites live in hostile environments in which they are challenged chemically and their hosts attempt in many ways to kill them. In response, the parasites have evolved multiple mechanisms that take advantage of these challenges to enhance their survival. Perhaps the most impressive example is the evolutionary co-option of DNA repair mechanisms by the parasites as a means to rapidly manipulate the structure, antigenicity, and expression of the products of specific multigene families. The purpose of variant proteins that mediate cytoadhesion has long been thought to be primarily the avoidance of splenic clearance. Based upon known biology, I present an alternative perspective in which it is survival of the oxidative environment within which spp. parasites live that has driven integration of DNA repair, antigenic variation, and cytoadhesion, and speculate on how genome organization affects that integration. This perspective has ramifications for the development of parasite control strategies.
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http://dx.doi.org/10.3389/fcimb.2022.869696 | DOI Listing |
EMBO Rep
January 2025
Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
Homologous recombination is a largely error-free DNA repair mechanism conserved across all domains of life and is essential for the maintenance of genome integrity. Not only are the mutations in homologous recombination repair genes probable cancer drivers, some also cause genetic disorders. In particular, mutations in the Bloom (BLM) helicase cause Bloom Syndrome, a rare autosomal recessive disorder characterized by increased sister chromatid exchanges and predisposition to a variety of cancers.
View Article and Find Full Text PDFExp Mol Med
January 2025
Section on DNA Repair, Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
RecQ helicases, highly conserved proteins with pivotal roles in DNA replication, DNA repair and homologous recombination, are crucial for maintaining genomic integrity. Mutations in RECQL4 have been associated with various human diseases, including Rothmund-Thomson syndrome. RECQL4 is involved in regulating major DNA repair pathways, such as homologous recombination and nonhomologous end joining (NHEJ).
View Article and Find Full Text PDFNat Commun
January 2025
Mechanisms, Biomarkers and Models Section - Genome Stability Group, Department of Environment and Health, Istituto Superiore di Sanità, Viale Regina Elena, 299 - 00161, Rome, Italy.
The WRN protein is vital for managing perturbed replication forks. Replication Protein A strongly enhances WRN helicase activity in specific in vitro assays. However, the in vivo significance of RPA binding to WRN has largely remained unexplored.
View Article and Find Full Text PDFCell Death Discov
January 2025
Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
TP53 mutations are recognized to correlate with a worse prognosis in individuals with non-small cell lung cancer (NSCLC). There exists an immediate necessity to pinpoint selective treatment for patients carrying TP53 mutations. Potential drugs were identified by comparing drug sensitivity differences, represented by the half-maximal inhibitory concentration (IC50), between TP53 mutant and wild-type NSCLC cell lines using database analysis.
View Article and Find Full Text PDFMelanoma Manag
December 2024
Supportive Care Dep, Institut Curie, Paris, France.
Metastatic uveal melanoma (UM) patients often initially present with limited symptoms despite a poor prognosis, complicating communication with patients and caregivers. Early Together (NCT04728113) is a randomized Phase III trial that integrates early palliative care through systematic joint visits involving the palliative care team and the medical oncologist, compared with standard oncological care, in 162 metastatic UM patients beginning systemic treatment. This collaboration aims to enhance patient functioning, improve quality of life and facilitate coping mechanisms.
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