Publications by authors named "Carlos Mendez-Dorantes"
Article Synopsis
- The LINE-1 retrotransposon is a significant genetic element in humans, contributing to about a third of our genome via a 'copy and paste' method driven by its enzyme, ORF2p, which is linked to diseases like cancer and autoimmunity.
- Recent studies using X-ray crystallography and cryo-electron microscopy have revealed new structural details of ORF2p, including previously unknown domains and a dynamic conformation that changes during the retrotransposition process.
- The findings enhance our understanding of L1 replication and its effects on immune responses, creating potential pathways for drug development targeting L1 and related cellular processes.
Article Synopsis
- LINE-1 is the only active protein-coding transposon in humans that uses RNA to insert itself into different locations in the genome, making up about 20% of our DNA.
- Most LINE-1 copies are inactive, but around 100 can move and are linked to the development of cancer due to their overexpression and retrotransposition.
- The text reviews how LINE-1 is regulated, its role in increasing genetic diversity in tumors, and potential treatments that could target LINE-1 activity in cancer therapies.
Article Synopsis
- Triple-negative breast cancer (TNBC) relies on external arginine for survival and has high levels of the protein BiP, which is linked to cancer spread and stress responses in cells.
- The study explored how reduced arginine affects BiP expression in the MDA-MB-231 TNBC cell line, creating two variants: one with normal BiP and another with a mutated version called G-BiP.
- Results indicated that low arginine levels hindered BiP translation, and cells with G-BiP showed greater resistance to arginine shortage, suggesting that targeting BiP could help manage TNBC growth during stress conditions.
Article Synopsis
- Researchers have discovered potential progenitor cells in the adult human pancreas that can self-renew and differentiate into various cell types, which could be beneficial for regenerative medicine.
- By using a special assay technique, scientists identified a subpopulation of ductal cells that can grow significantly and produce insulin-expressing cells when treated with specific inhibitors.
- These findings suggest that progenitor-like cells either naturally exist in the adult pancreas or can easily adapt and thrive in a lab setting, opening avenues for treatment in diabetes and other conditions.
Long interspersed element 1 (LINE-1) open reading frame 1 protein (ORF1p) expression is a common feature of many cancer types, including high-grade serous ovarian carcinoma (HGSOC). Here, we report that ORF1p is not only expressed but also released by ovarian cancer and primary tumor cells. Immuno-multiple reaction monitoring-mass spectrometry assays showed that released ORF1p is confidently detectable in conditioned media, ascites, and patients' plasma, implicating ORF1p as a potential biomarker.
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- CRISPR/Cas9 has transformed molecular biology and entered gene therapy, making it important to track DNA changes for safe and effective editing.
- Researchers found that LINE-1 retrotransposons can frequently insert themselves at CRISPR/Cas9 target sites, demonstrating over 2500 new insertions in various cell types.
- Unlike CRISPR/Cas9, other editing methods like prime editors and base editors result in rare L1 insertions due to lower DNA break rates, highlighting differences in safety profiles among these editing tools.
LINE-1 expression in cancer correlates with p53 mutation, copy number alteration, and S phase checkpoint.
Proc Natl Acad Sci U S A
February 2022
Retrotransposons are genomic DNA sequences that copy themselves to new genomic locations via RNA intermediates; LINE-1 is the only active and autonomous retrotransposon in the human genome. The mobility of LINE-1 is largely repressed in somatic tissues but is derepressed in many cancers, where LINE-1 retrotransposition is correlated with p53 mutation and copy number alteration (CNA). In cell lines, inducing LINE-1 expression can cause double-strand breaks (DSBs) and replication stress.
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- Chromosomal double strand breaks (DSBs) trigger various signaling pathways, but the role of these signals in DSB repair is not fully understood.
- An RNA interference study revealed that the E3 ubiquitin ligase RNF8 inhibits deletion rearrangements through canonical non-homologous end joining while promoting alternative end joining (ALT-EJ) events.
- RNF8's involvement in repair processes is nuanced; it facilitates limited end resection repairs linked to KU but supports homology-directed repair (HDR) through a separate mechanism that enhances PALB2 function.
Article Synopsis
- * The study found that the RAD52 S346X variant is associated with a decreased breast cancer risk in BRCA2 carriers (HR = 0.69) and a lesser extent in BRCA1 carriers (HR = 0.78).
- * The RAD52 S346X mutation impairs DNA double-strand break repair, which may explain why it reduces cancer risk in BRCA2 mutation carriers.
Article Synopsis
- - The research focuses on repeat-mediated deletions (RMDs) triggered by DNA double-strand breaks (DSBs) and how factors like repeat sequence divergence and DSB/repeat distance impact these deletions.
- - BLM helicase aids RMDs when there are long distances between DSBs and repeats, likely due to its role in extensive DSB end processing, while it suppresses RMDs with intermediate distances and sequence divergence, indicating its function in rejecting heteroduplexes.
- - The influence of BLM on RMDs varies significantly based on DSB/repeat distance and the divergence of repeat sequences, and its role in heteroduplex rejection operates independently of other factors like MSH2 and
Article Synopsis
- 53BP1 promotes genome instability and cell death in BRCA1-deficient mice by hindering the process of homologous recombination (HR), crucial for DNA repair.
- The interaction of 53BP1 with PTIP and the RIF1/shieldin complex is essential for its anti-recombinogenic effects, but how PTIP specifically hinders HR is not fully understood.
- Mutating a specific site in 53BP1 can alleviate the lethality in BRCA1-deficient mice by enhancing DNA damage processing, but this leads to HR failure due to excessive shieldin activity blocking necessary proteins for repairing DNA.
Evidence for interaction between Hsp90 and the ER membrane complex.
Cell Stress Chaperones
September 2018
Article Synopsis
- Recent studies have identified various proteins interacting with heat shock protein 90 (Hsp90), suggesting they might be new clients or co-chaperones involved in protein folding.
- High-throughput screens in yeast revealed genetic links between Hsp90 and the endoplasmic reticulum membrane complex (EMC), crucial for managing stress from unfolded proteins.
- Experimental findings confirm a functional relationship between Hsp90 and EMC, showing that interactions affect growth and drug tolerance, as well as proper folding of Hsp90 target proteins.
Article Synopsis
- Scientists studied how certain DNA changes happen when parts of the DNA are repeated and far apart.
- They found that cutting the DNA with two breaks can cause these changes, and moving one of the cuts further away only slightly affects how often the changes occur.
- Some proteins in cells help stop these changes, while others make them happen more easily, and even small differences in DNA sequences can affect the likelihood of these changes.