Critique for article: TRF1 phosphorylation on T271 modulates telomerase-dependent telomere length maintenance as well as the formation of ALT-associated PML bodies (Article Critique Sample)

Critique for article: TRF1 phosphorylation on T271 modulates telomerase-dependent telomere length maintenance as well as the formation of ALT-associated PML bodies
Abstract:
Cancer cells have the characteristic of rapid uncontrolled cell proliferation without entering the cell senescence. This is accomplished by either their high expressing level of telomerase or by the telomerase-independent mechanism, called the alternative lengthening of telomere (ALT). C-circles and ALT-associated PML bodies (APBs) are characteristics of the ALT mechanism. The hypothesis of this article was that there is a novel TRF1 (a subunit of shelterin complex that involved in both mechanisms) phosphorylation site at position threonine 271 that can modulate both the telomerase-mediated telomere lengthening pathway and the ALT pathway. The authors found that the phosphorylation on T271 of TRF1 negatively regulated the telomerase-dependent mechanism, meanwhile facilitate the association of TRF1 with the telomeric DNA. In telomerase-independent ALT cells, they found the phosphorylation on T271 is required for APB formation but is not necessary for C-circle production. Overall, this article provided strong evidence toward the main question and findings that in agreement with previous research. Controls and stable cell lines are used with proper techniques to analyze the data. This research was generally well-written with minor misinterpretations, the use of unpublished content and minor error in the wording and structure of the paper.
Introduction:
Cancer cells gain their uncontrolled cell proliferation characteristic by the maintenance of their telomere length (Artandi & Depinho, 2009). Telomeres are specialized highly repetitive DNA sequence of many kilobases of TTAGGG found at the end of linear eukaryotic chromosomes (Shay & Wright, 2011). They serve as protective role in the end replication problem which is a phenomenon of the inability of DNA polymerase to replicate the very end of the chromosome (Neumann & Reddel, 2002). The continuous cell proliferation will lead to cell crisis, in which the cells have critical shortened telomere that lead to the entry of replicative senescence (Shay & Wright, 2011). Thus, to avoid the replicative cell senescence, the activation of the telomere lengthening mechanism is indispensable for the immortalization characteristic of cancer cell (Neumann & Reddel, 2002). About 85-90% of human cancer uses the activation of telomerase (Shay & Bacchetti, 1997) and the remaining 10-15% of human cancer cell uses the alternative lengthening of telomeres (ALT) in a homologous recombination-based manner (Cesare & Reddel, 2010)