Diana Marcela Grecco Herrera

Medicine student

*ACT is a control of high precision RNA synthesis, a reliable copy depends on it. Is an intern change of RNA polymerase.

*B cell lymphoma is a Non-Hodgkin lymphoma, is a heterogeneous group of lymphoproliferative malignancies.

*E. Sosunova, V. Sosunov, et al. Control of transcription

fidelity by active center tuning as derived from RNA

polymerase endonuclease reaction. Journal of Biological

Chemistry, 2013; DOI: 10.1074/jbc.M112.42400

2

*In RNA polymerase the functionally state of the ACT works with two Mg ions coordinated by an aspartate triad

*ACT turn on when: you have to correct NTP substrates or you have free RNA residues. (Need an internal change)

*Transcript scission Gre factors provides an ACT stabilization to Mg ions and strongly reinforce the proofreading.

*The mechanism of DNA polymerase has 2 different active centers sites to synthesis and proofreading. (Doesn´t need an internal change)

DNA polymerase

active center are

carboxylates stem from

rigid scaffolds

Multisubunit RNA

polymerase have a flexible loop. ACT has an important re-shaping of

the loop.

*I think that it is important to investigate the process that can influence in an

replication or the transcription of the DNA, because if we find out the process in which it went wrong, we can make a

treatment specially designed to repair or even heal the DNA malfunction. The first step is to investigate the process, as the

researchers made here.

*Jacqueline H. Barlow, Robert B. Faryabi, et al. Identification of Early

Replicating Fragile Sites that Contribute to Genome Instability. Cell, 2013;

DOI:10.1016/j.cell.2013.01.006

*The B lymphocytes are among the most rapidly dividing cells resulting in a risk of replication-induced DNA damage.

*Double-strand breaks at fragile sites as repetitive sequences that are hard to copy, this happen when DNA is replicated prior to cell division.

*B-cell have the activation-induced cytidine deaminase (AID) which causes collateral damage in the genome in the non-replicative stage of the cycle.

*AID-independent source of DNA breaks that is associated with replication which is also called an early replicating fragile sites (ERFSs).

*DNA damage occurs at ERFSs in thee early stages of replication.

ERFSs overlapped with DNA alterations associated with B cell

lymphoma

*Locate ERFs as possible point of the beginning of the B cell lymphoma, which can impulse the investigation of cancer cures to this kind or ways to handle the

sickness. Furthermore it can give clues to work with other kind of cancer.

*By investigating we can change the current diagnostic and treatment of genetic malfunctions, by giving opportunities to controling the, as a molecular level, as the processes of these cell.

study the mechanism of

control of replication and transcription

*The "ACT" gives the investigators a molecular blank to avoid the DNA damage.

ACT

Tool that let you

control the fidelity of

the replication

*Find out how B cell lymphoma acts and start helping in the therapeutic area Giving basis in developing drugs.

*The replication-induced DNA damage could be used by many kind cancer to arise.

The results of the study can be used to investigate

different kinds of cancer.

*· [http://www.sciencedaily.com/releases/2013/01/130115111109.htm] checked on February 4th of 2013. “ New Paths Explored for Curbing Genetic Malfunctions”

*· [http://www.sciencedaily.com/releases/2013/01/130124123307.htm ] checked on February 5th of 2013. “Discovery of New Class of Damage-Prone DNA Regions Could Lead to Better Cancer Treatments”

*· [http://emedicine.medscape.com/article/202677-overview] Checked on February 8th of 2013. “B-cell Lymphoma”

“Some people want it to happen, some wish it would happen, others make it happen.” M.

Jordan.