Telomerase Cancer And Aging Flashcards
Joins chromatids together
Centromere
- Double Stranded DNA
- Long arm (q)
- Short arm (p)
Chromatids
•Found at each end of Chromatid
Telomere
Condensed regions within the chromosome that are responsible for the accurate segregation of the replicate
Centromere
- Short thymine-guanine sequence
* 5’-TTAGGG-3’ Sequence
Telomere
Found at each end of a chromatid, which protects the end of the chromosome from deterioration or from fusion with neighbouring chromosomes
Telomere
are the sites at which DNA synthesis is occurring
• New chains grow 5’-3’
• Bidirectional
• Semi-conservative
Replication forks
- Made up of 6 proteins arranged in a ring shape
- Motor proteins
- Unpackage an organism’s gene
Unwinding
Helicase
- Tetramers
* Attached to the post-replication fork single strands of DNA, preventing their “reannealing“
Single strand binding proteins
- A type of RNA Polymerase
- Creates a RNA Primer
- Key importance in DNA Replication
Primase
• Creates DNA Molecules by assembling nucleotides
DNA polymerase
- Non- Specific Endonuclease that catalyzes the cleavage of RNA
- Removing the RNA primer
RNase H
• A ligase that facilitates the joining of DNA strand together by catalyzing the formation of a phosphodiester bond.
DNA ligase
During chromosome replication, the enzymes that duplicate the DNA cannot continue duplicating all the way to the end of the chromosome
Lagging strand
Okazaki fragments
attached ahead on the lagging strand
RNA primer
It is the phase or stage in which normal cells cease to divide
Cellular senescence
Mas mahaba nag telomer
Mas mahaba ang buhay
Cellular senescence
Telomere shortening
A section of telomeres is lost during each cycle of
Replication
is the result of a sugar reducing molecule, such as fructose or glucose, bonding to a protein or Lipid molecule without the controlling action of an enzyme.
Glycation
Senescence involve what pathways? That lead to cancer, kasi hindi mamatay yung mga cell
p53 and pRb pathways
is an enzyme that adds telomeric sequences to the ends of each chromosome
Telomerase
telomerase is a combination of a
Protein and RNA
present in most fetal tissues, normal adult male germ cells, stem cells, in proliferative cells of renewal tissues, and in most tumor cells
Telomerase
Protein component of telomerase
human Telomerase Reverse Transcriptase
human Telomerase RNA (hTR or hTERC)
RNA component of telomerase
MECHANISM OF TELOMERIC LENGTHENING
Binding
Elongation
Translocation
Elongation
- stabilizes the telomere
- prevents the telomere ends from being recognized as break points by the DNA repair machinery thus it gives protection from exonucleases.
- preventing the telomere from eliciting a DNA damage response manifested as cell-cycle arrest or apoptosis
T loop
- It binds along the length of the T-loop.
- along with TRF2, it normally prevents telomerase from adding more telomere units to telomeres.
- But when telomere lengthening is required, TRF1 recruits helicases to facilitate the process.
TRF1
- It appears to promote formation of D-loop
- prevents ataxia telangiectasia mutated (ATM) activation, which is a DNA damage response (DDR) to DNA double strand breaks.
- But when DNA repair of telomeres is required, TRF2 recruits DNA repair proteins.
TRF2
- links TRF1 with TRF2, and connects both to TPP1 .
- TIN2 is believed to facilitate recruitment oft single-stranded telomere-binding proteins to telomeres.
- TIN2 interacts with TRF1 and has been suggested to stabilize the T-loop.
TIN2
- only binds to the single-stranded 3’-end DNA overhang.
- POT1 prevents ataxia telangiectasia and Rad3 related (ATR) activation, which is a DNA damage response (DDR) to DNA double strand breaks.
- Humans only have a single POT1, whereas mice have POT1a and POT1b.
POT1
- binds to TRF2, and facilitates TRF2 function.
- RAP1 protects telomeres from non homologous end joining (NHEJ).
- Unlike the other shelterin proteins, RAP1 has functions independent of its function within the shelterin complex: RAP1 regulates transcription and affects NF- kb signaling.
RAP1
- interacts with POT1 and regulates its function.
- When telomeres are to be lengthened, TPP1 is a central factor in recruiting telomerase to telomeres.
- Deletion of TPP1 from shelterin elicits an ATR-mediated DDR.
TPP1
is a good biomarker for cancer detection because most human cancers cells express high levels of telomerase.
Telomerase
Kapag maigsi, maigsi din ang buhay.
Nagpapahaba ng buhay ng cell, lalo na ang cancer cell
Telomere
Telomerase
