News Highlight
DNA damage recognition: keeping the right players on board
DNA breaks are an unfortunate consequence of the biochemical processes that keep our cells alive. Thankfully, we are well equipped to deal with these potentially lethal changes with a cascade of DNA damage recognition and repair mechanisms that kick in when a break is detected.
Genomic DNA is continually being damaged. This figure shows the types of damage that can occur
Dr Nick Lakin and his group, in collaboration with colleague Dr Catherine Pears, have recently published a paper that describes some of the intricate processes that facilitate repair of DNA breaks (1). Their work has implications for cancer research, where there is a strong interest in developing treatments to exploit the weakness in DNA damage repair that cancer cells frequently show.
Lifecycle of Dictyostelium discoideum(Strmecki et al (2005). Dev Biol. 284, 25-36)
(Click to enlarge)
The two researchers use Dictyostelium discoideum, a simple haploid eukaryote, to study DNA repair pathways. Dictyostelium is an attractive model system because it can be manipulated genetically and has DNA repair enzymes similar to those found in humans. These enzymes are equipped to repair both DNA single-strand breaks and double-strand breaks (DSBs).
‘We are interested in enzymes called PARPs which function in signalling DNA damage,’ explains Dr Lakin. ‘Their role is best defined in the repair of single-strand DNA breaks. They are also part of an early response to DSBs, but nobody knows what they do here.’ |
PARPs [poly ADP-ribose (PAR) polymerases] are recruited to the site of damage and catalyse addition of a polymer of ADP-ribose unit onto proteins, Their targets are not known, but PARylation, as this addition is known, is thought to relax the chromatin structure around the break, possibly enabling access of repair proteins to the site of damage. The polymers also provide interaction domains for other proteins, a process that is likely to be important for recruiting and retaining repair components at sites of DNA damage.
