Andy Coghlan does a great job of explaining what gene recombination is and why it’s important – it’s one of the main processes that make people different from one another, despite the fact that the majority of our DNA is the same.
Recombination is what happens during the development of gametes; our sex cells (sperm and eggs). The process of cell division alters from mitosis (where cells split into two cells with the usual complement of DNA) to meiosis, in order to generate cells with half the DNA complement, so that when the two sex cells combine, you get the correct amount of DNA in the zygote.
We could almost imagine chromosomes (strings of DNA containing our genes) as cards, as suggested in the NS article, and this PRDM9 enzyme as the dealer in the cellular casino.
During meiosis, the parental chromosomes do a bit of shuffling and also rearrangement in the form of chromosomal crossover to produce a new ‘half-deck’ ready for the next generation; making offspring different from their parents.
PRDM9 grabs hold of the chromosomal ‘cards’ with a zinc finger structure; a fairly common way for amino acids in a protein to fold together, allowing the protein to bind to DNA.
The nature of this finger structure, its fingerprint if you like, means it recognises certain motifs in the DNA; patterns of DNA bases that act like beacons – directing proteins to their binding sites.
The DNA motifs bound by PDRM9 seem to be around ‘hot spots‘ on sperm chromosomes, meaning that wherever PDRM9 binds to DNA, it’s likely that the strand will break and stick to another strand – a bit like ripping the 5 of clubs in half and sticking it to half of the 8 of hearts.
So, what you get at the end is a nicely mixed-up deck!
This enzyme’s activity seems to be very important both in the normal meiotic processes of chromosomal rearrangement and also in some cases where it goes wrong.
Chromosomal instability (CIN) is important in some diseases, including cancer, and occurs when chromosomes break and re-join when they should not. Cancer cells often have very abnormal karyotypes (the chromosomal arrangement in the cell) and understanding what causes this could be useful in developing new anti-cancer therapies.
So it is likely that we will hear of PDRM9 again; to understand the game you need to know the house rules and PDRM9 seems to be playing an important part in deciding them.