Aligning and repairing broken chromosomes
The human genome consists of 23 pairs of homologous chromosomes, which together amount to a total of six billion base pairs of DNA sequence. This vast repository of information encodes all of the instructions necessary to make a human being. However, chromosomes can be damaged by cytotoxic agents in the environment, such as carcinogenic chemicals or ionizing radiation, or even by natural cellular process. Double strand DNA breaks (DSBs) are among the most toxic of DNA lesions because they can lead to chromosomal rearrangements, which are a hallmark of all forms of cancer. Fortunately, rather than simply succumbing to this onslaught of damage, our cells have the ability to repair broken chromosomes. Homologous recombination (HR) is an important error-free pathway that allows our cells to use sequence information encoded within the homolog as a template to guide repair of broken chromosomes. However, for this to occur, members of the RecA/Rad51 family of recombinases must first search through vast amounts of DNA to align the broken chromosome ends with the undamaged template. In a recent study published in Cell, Qi et al. used single-molecule imaging to visualize how this takes place (http://www.cell.com/cell/fulltext/S0092-8674%2815%2900072-0). They demonstrated that the Rad51/RecA family of recombinases align DNA sequences by making use of a length-based search mechanism that enables rapid identification of 8-nucleotide (nt) tracts of microhomology. This remarkable process confines the search to sites with a high probability of being a homologous target while ignoring the rest of the genome. These findings provide new insights into how broken chromosomes are aligned during repair.
Dr. Zhi Qi received his doctorate in Biophysics from the University of Illinois in 2012, and his thesis research was conducted in the laboratory of Dr. Yann Chemla. He joined the laboratory of Dr. Eric Greene (University of Illinois, Class of ‘94) at Columbia University as a Postdoctoral Research Associate in 2013.