Newly found protein plays vital role in cancer development
Scientists from the University of Michigan have reported that they have found a key protein that plays a vital role in the development of cancer.
“Most proteins involved in responding to DNA damage that can cause cancer either help detect the damage and warn the rest of the cell, or help repair the damage,” said David O. Ferguson, MD, PhD, who led the research team.
Previous research have shown that the protein Mre11 functions as a “gatekeeper” — it prevented damaged cells from proliferating. Now, UM researchers have found that in mammals, a function of the Mre11 protein also serves as a “caretaker,” by repairing DNA.
Naturally, the cells in our body grow, divide and eventually die. When something damages a healthy cell’s DNA, such as radiation for example, a multi-protein complex steps in to repair the breakage and activate other fundamental cellular processes.
The MRN complex, made out of the Mre11, Rad50 and NBS1 proteins, senses DNA damage, known as double-strand breaks, within the cell. The complex then transmits that information to an enzyme called the ATM (ataxia-telangiectasia mutated) checkpoint kinase.
The ATM kinase controls the cell’s response to double-strand breaks, and slows cell growth to give the cell opportunities to repair them.
When the MRN complex doesn’t work properly, inherited human neurological diseases, such as ataxia-telangiectasia-like syndrome and Nijmegen breakage syndrome, result. Both feature MRN mutations and significantly predispose a person to immunodeficiency and cancer.
“This may have implications for diagnoses because tumors associated with different mutations may have different prognoses and respond to different therapies,” he says. In particular, mutations in Mre11 may predict how sensitive or resistant a particular tumor will be to treatments with DNA-damaging agents. The fact that we have now separated the functions of DNA repair from the checkpoint functions means we may have identified a target that can sensitize tumors to radiation and chemotherapeutic agents used in treating cancer,” said Ferguson.
The details are published in the journal Cell. The research was funded by National Institutes of Health, the Sidney Kimmel Cancer Research Foundation and the University of Michigan Cancer Center Support Grant and Munn Endowment.
Source: med.umich.edu
