DNA Repair MechanismsMaria Fernanda Sánchez Rico

Third Semester

Medicine – UPB

2010

Folding

Folding

IntroductionCells have the

ability to detect and repair the

damage that DNA might suffer.

When DNA sequence is damaged and left

uncorrected, the cells can accumulate

mutations and function improperly.

To prevent these kinds of failures, the cell has DNA repair

mechanisms .

Researchers identify DNA damage repair gene in Fanconi

anemia pathwayNewswire The Rockefeller University

(July 20, 2010)

Researchers identify DNA damage repair gene in

Fanconi anemia pathway

•Protein associated with Fanconi Anemia (FA) might be involved in repairing inter-strand crosslinks in DNA.•When one of the proteins in the FA pathway is damaged, the result is Fanconi Anemia, which can cause various forms of cancer.

Researchers identify DNA damage repair gene in

Fanconi anemia pathway

•FAN1 has important properties to repair DNA

Encodes a nuclease

Has a UBZ domain that binds ubiquinated proteins

Researchers identify DNA damage repair gene in

Fanconi anemia pathway

•FAN1 holds onto sites of the DNA damage•The nuclease domain can cut DNA•FAN1’s restorative ability lie in the capacity to interact with ubiquinated proteins.

Observation

Drug that Inhibits DNA-repair Enzyme Shrinks Some Breast and

Ovarian TumorsNCI Cancer Bulletin

(July 13, 2010)

Drug that Inhibits DNA-repair Enzyme Shrinks

Some Breast and Ovarian Tumors

•The drug Olaparib blocks a DNA repair enzyme called PARP•Two phase II clinical trials were made to prove that olaparib shrinks tumors in women with inherited BRCA1 or BRCA2 mutations

Drug that Inhibits DNA-repair Enzyme Shrinks

Some Breast and Ovarian Tumors

In the first clinical trial 54 women with breast cancer and BRCA1 or BRCA2 mutations participated.•27 women received 400mg of olaparib twice a day tumors shrank in 11 women in this group.•27 women received 100mg of olaparib twice a day tumors shrank in 6 women in this group.

Drug that Inhibits DNA-repair Enzyme Shrinks

Some Breast and Ovarian Tumors

In the second clinical trial 57 women with ovarian cancer and BRCA1 or BRCA2 mutations participated.•33 women received 400mg of olaparib twice a day tumors shrank in 6 women in this group.•24 received 100mg of olaparib twice a day tumors shrank in 3 women in this group.

Observation

Medical Utility

Medical Utility

•The study of DNA repair mechanisms is very promising to reduce the incidence of cancer.

Medical UtilityResearchers identify DNA damage repair gene in

Fanconi anemia pathway

•The discovery of FAN1 could probably hold the key to improve the lives of those who have Fanconi Anemia, avoiding the incidence of cancer in these patients.•FAN1 might also be related with multiple types of cancer.

Medical UtilityDrug that Inhibits DNA-repair Enzyme Shrinks

Some Breast and Ovarian Tumors

•Olaparib could become a way of treatment for cancer patients that have resistant tumors.•This drug may perhaps provide a longer life and stabilize the disease.

Bibliography

• MARTINEZ SANCHEZ, L. Biología Molecular. Libro de case. Quinta edición. Medellín: UPB 2009.

• LODISH, Harvey. Molecular Cell Biology. 5th Edition. W.H. Freeman, 2008.

• Researchers identify DNA damage repair gene in Fanconi anemia pathway. The Rockefeller University Newswire[internet magazine] 2010 20 July [consult date July22, 2010]. Available on: http://newswire.rockefeller.edu/?page=engine&id=1084

• Drug that Inhibits DNA-repair Enzyme Shrinks SomeBreast and Ovarian Tumors. NCI Cancer Bulletin[internet magazine] 2010 13 July [consult date July22, 2010]. Available on: http://www.cancer.gov/ncicancerbulletin/071310/page3

Thank You!!!