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生物论文代写:The End Replication Problem Of Cellular Senescence

生物论文代写:The End Replication Problem Of Cellular Senescence

Cellular senescence is the barriers that protecting our cells from undergoing abnormal proliferation. However, there are many factors that can induce the cellular senescence such as, DNA damage and telomere shortening ( Campisi J, 2005) . Study by Dr. Leonard Hayflick and Dr. Paul Moorhead, showed that human cells have a limited capacity to grow in culture by dividing. They showed that, human cells derived from newborn tissue, embryonic and fetal can divide from 40 to 60 times, but then can’t divide more than that. However, the number of cell divisions is called Hayflick Limit ( Maity and Koumenis,2006).

Nowadays, scientists believe that the determination of the Hayflick Limit is the length of human telomeres. Telomeres are the end part of chromosomes. When the cell divides, it must to double its chromosomes. Results in each daughter cell have a full complement of genetic materials. When the cells double the chromosomes, in each time the chromosomes lose a little bit of its telomeres. After 40 to 60 times of cells divisions, the telomeres have reached a critically short length, the replication of chromosomes will stop and no longer cell dividing. So, the cells that have shortened telomeres and can’t divide called senescent.

The end replication problem:

Several studies shows that, the process of semi-conservative replication of DNA works only in the 5′ to 3′ direction, and the DNA polymerase needs binding with an RNA primer. (Smeal et al., 2007) Scientists predicated the characteristic of the consequences of DNA replication and they termed it the end-replication problem. However, the loss of a small 5′ nucleotide segment because of the DNA synthesis took place and with repeated replication the telomere become shorter.

Telomeres and telomerase:

Telomeres are located at the end of liner chromosomes, and are composed of repetitive DNA sequences. There are 92 telomeres in humans because 23 chromosomes and in each end of each chromosome one telomeres. Hence, each human telomere has thousands of repeats of the six nucleotide sequence, TTAGGG. The hypothesis of aging and cancer based on the telomere-telomerase shows that most human somatic cells don’t have telomerase activity, whereas most human tumours have telomerase activity. However, the balance between the end-replication problem and telomerase maintained the telomere length. Telomerase can be defining as a cellular reverse transcriptase (a ribonucleoprotein enzyme complex) which is referred to as a cellular immortalizing enzyme. It maintains the telomere length by adding hexameric (TTAGGG) repeats onto the end of the chromosomes. Telomerase has ability to reinstate lost telomeri DNA- repeat sequence, which can help cells to bypass replicative senescence and may confer cellular immortality. (Beitzinger et al., 2006) There is evidence that replicative senescence of human cells is due to telomere shortening. (Vijji et al., 2007)

The two crucial constituents of telomerase consist of two enzymes, a human telomerase reverse transcriptase (hTERT) and an RNA template molecule which has a complimentary to the human telomeric DNA (hTR). However, hTERT is the primary rate-limiting component of telomerase, and hTR can be limiting for telomere maintenance. Telomerase is protecting germ line cells against telomere shortening. Studies show that, telomeres of human germ line cells are maintained at about 15 kbp. In contrast, in most somatic cells that undergo more than 40-80 times of cellular replicative senescence, telomerase is not expressed in these cells, with the considering of telomere shorting. Whereas, the expression and activity of telomerase in tumours cells and transformed cells is very high. (Vincent et al., 1992; Koji et al., 2001)

生物论文代写:The End Replication Problem Of Cellular Senescence