In a new paper published in Nature, researchers have outlined the structure and function of a protein complex which is required to repair damaged DNA and protect against cancer.
Every time a cell replicates, mistakes can happen in the form of mutations, but specialised proteins exist to repair the damaged DNA.
People with mutations in a DNA repair protein called BRCA2 are predisposed to breast, ovarian and prostate cancers, which often develop at a young age. In the clinic, these cancers are treated with a drug that inhibits PARP, another protein needed for DNA repair.
Recent work shows that defects in several other proteins can cause inheritable breast and ovarian cancers or Fanconi anaemia, a blood disorder that can lead to different cancers, including leukaemia.
The researchers used cryo-electron microscopy to reveal the atomic structure of four of these proteins, which come together to form a complex called BCDX2. This allowed them to map mutations associated with cancer on the 3D structure, revealing the important regions of the complex, and why certain mutations prevent DNA repair, leading to an instability in a person’s genes and cancer.
In addition, the researchers discovered BCDX2’s role in the cell, finding that it acts as a ‘molecular chaperone’ – it helps target another protein called RAD51, causing it to recognise and assemble at regions where DNA repair needs to take place. Together, BRCA2, BCDX2 and RAD51 are the main players in the process that repairs damaged DNA – called ‘homologous recombination’.
The research shows that BCDX2 is just as important for repairing DNA as BRCA2, suggesting mutations should also be routinely screened for.
A co-first author and postdoctoral research assistant, said: “For the first time, we’ve been able to show the direct links between structure, function and why mutations in any of the components of BCDX2 leads to cancer. We now understand its crucial role in DNA repair, which explains why mutations can lead to cancer.”
The research today could help inform the best line of treatment for people living with cancer.
A group leader of the DNA Recombination and Repair Laboratory, said: “BRCA2 is well characterised and known to increase the risk of cancer, especially breast and ovarian cancers. It’s mutated in 15-20% of inheritable cancer cases so is regularly screened for.
“Our research has shown that BCDX2 is also crucial for DNA repair and acts in the same pathway as BRCA2. For people with cancers caused by defects in BCDX2, PARP inhibitors are also likely to be effective. Our findings suggest that people with a family history of these cancers should be screened for mutations in the proteins making up BCDX2 to get a full picture of their risk.”
The researchers are now hoping to shed light on another protein complex, CX3, which is also involved in cancer. Putting all these insights together will allow a better understanding of genes which put people at a greater risk of cancer and help with targeted treatment.
https://www.nature.com/articles/s41586-023-06179-1
Mechanism of protection against breast and ovarian cancer
- 1,043 views
- Added
Latest News
Tumor infiltration of immun…
By newseditor
Posted 28 May
New light-controlled 'off s…
By newseditor
Posted 28 May
Gene function during embryo…
By newseditor
Posted 28 May
Formation of 3D blood vesse…
By newseditor
Posted 27 May
Liver regeneration during c…
By newseditor
Posted 27 May
Other Top Stories
How the bacterial endotoxin LPS prevents or promotes allergic disease
Read more
Genetic mechanism enables bacterial communities to organize into so…
Read more
How gut microbiota triggers inflammation from toothpaste compound t…
Read more
Epstein-Barr virus may be leading cause of multiple sclerosis
Read more
How bamboo diet keeps giant panda chubby
Read more
Protocols
SEMORE: SEgmentation and MO…
By newseditor
Posted 26 May
Spatially resolved lipidomi…
By newseditor
Posted 24 May
Efficient expansion and CRI…
By newseditor
Posted 21 May
Massively parallel in vivo…
By newseditor
Posted 20 May
Breast cancer-on-chip for p…
By newseditor
Posted 16 May
Publications
I Am Curious About Cannabis…
By newseditor
Posted 30 May
Advanced microbiome therape…
By newseditor
Posted 29 May
Hippocampal astrocytes indu…
By newseditor
Posted 29 May
TNIK's emerging role in can…
By newseditor
Posted 29 May
Diabetes drugs activate neu…
By newseditor
Posted 29 May
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar