Today we have concluded a meeting with DR Zhang and (UTEP) and DR Bryan (Texas Tech) on future projects. We have discussed our collaborative efforts on several projects, and discussed to use "gene interference" techniques to affect several genes and see whether we can affect several pathways for the cure of cancer.
Several critical areas:
ie. Could blocking PMS2 (MLH-1 or MLH1 protein ) increase the efficiency of 5-FU in Colon cancer?
ie. Could activation of ARF amplify MDM2 with increased proteosomal degration of P53 in certain Sarcoma?
ie. Could a genetically engineered AATCC Nucleotide set keep Telomeres busy to increase Apoptosis?
ie. Could genetic instability induced by inactivation of telomerase increase radiation sensitivity and response to certain chemotherapy agents?
ie. Examining the role of RPTPs in Alzheimer dementia
ie. Blocking the Farnesyl to delocalize RAS in lung cancers
ie. Blocking Phospholipase C in PIK3 driven cancers?
The meeting was concluded with a tour of the Laboratory.
Our work is cut out, CRBCM, is still working hard for the cure, no stone will stay unturned!
RTEL1 Is a Replisome-Associated Helicase That Promotes Telomere and Genome-Wide Replication
- Jean-Baptiste Vannier1,*,
- Sumit Sandhu2,*,
- Mark IR. Petalcorin1,
- Xiaoli Wu2,
- Zinnatun Nabi2,
- Hao Ding2,3,†,
- Simon J. Boulton1,†
+ Author Affiliations
- ↵†Corresponding author. E-mail: dingh@cc.umanitoba.ca (H.D.); simon.boulton@cancer.org.uk (S.J.B.)
-
↵* These authors contributed equally to this work.
Regulator of telomere length 1 (RTEL1)
is an essential DNA helicase that disassembles telomere loops (T loops)
and suppresses
telomere fragility to maintain the integrity of
chromosome ends. We established that RTEL1 also associates with the
replisome
through binding to proliferating cell nuclear
antigen (PCNA). Mouse cells disrupted for the RTEL1-PCNA interaction
(PIP mutant)
exhibited accelerated senescence, replication
fork instability, reduced replication fork extension rates, and
increased origin
usage. Although T-loop disassembly at telomeres
was unaffected in the mutant cells, telomere replication was
compromised,
leading to fragile sites at telomeres. RTEL1-PIP
mutant mice were viable, but loss of the RTEL1-PCNA interaction
accelerated
the onset of tumorigenesis in p53-deficient
mice. We propose that RTEL1 plays a critical role in both telomere and
genome-wide
replication, which is crucial for genetic
stability and tumor avoidance.
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PLEASE GO TO THE FULL ARTICLE,
GOOD JOB FOR THESE SCIENTISTS!
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PLEASE GO TO THE FULL ARTICLE,
GOOD JOB FOR THESE SCIENTISTS!