When a cell in our body divides, the resulting two cells should inherit exact copies of the same genetic material or DNA. This is extremely important, as the same genetic material must be passed on to the next generation, intact and unchanged. In daily life, a cell experiences different types of trauma or insults that can affect the structure of the DNA causing it to break. Environmental agents like UV irradiation or exposure to cancer causing chemicals among others can cause such damage. Many natural events occurring in our body can also contribute to stress in cells leading to DNA breakage.
If this broken or damaged DNA is not fixed, chances are we can lose chunks of DNA fragments. If this happens, important genetic information is lost when the cell divides. Therefore it is of utmost importance that the cell fixes or repairs this broken DNA before it decides to divide.
How does the cell deal with such stress?
The cell responds by giving out an SOS signal known as DNA damage response. Think of this as a 911 call in an event of emergency. The first responders here are the damage sensing proteins. These proteins accumulate at the site on DNA where damage has occurred. Their job is to assess and identify the type and extent of damage. These first responders then communicate with other proteins in the cell so that immediate measures to fix the damage can be taken.
With the receipt of the message, the DNA repair proteins will rush to the site of DNA breaks and carry out repair. Meanwhile, a set of proteins will make sure that the cell does not divide and halt the cell division process, effectively causing cell cycle arrest. As the repair process is complete and the broken DNA is fixed, halt on cell division is released. The cell can now go back to its normal state and continue its normal function.
However, if the extent of the damage is massive and the proteins fail to repair the broken DNA, there are proteins which will ensure that cell will be swiftly killed.
Why is DNA damage response important?
If the cell does not repair the DNA breaks in an efficient manner, the composition of DNA can get altered and result in mutations. If this goes unchecked and the cell continues to divide it can subsequently give rise to cancerous cells. This is indeed the case in many cancers where, the proteins assigned for DNA damage response fail to function properly. For example, BRCA1 is a protein important in DNA damage response and one of its roles is DNA repair. Damaged or mutated BRCA gene makes a defective BRCA1 protein resulting in inefficient DNA repair. This increases the risk of cancer especially, breast and ovarian cancer in women.
The DNA damage response system works to set up multiple levels of checkpoints incase of stress. Optimal functioning of components in this system is important for maintaining a healthy genome and providing a failsafe mechanism against increasing susceptibility to cancer.
Written and illustrated by Amrita Sule (@dramritasule). Edited by IndSciComm. Dr Sule works at the Virginia Commonwealth University on DNA damage response in cancer therapy.