BCD #3 - Non Homologous End-Joining (NHEJ)

Before I continue the last post discussion, I would like to say... INDEED!!! the universe has a funnily mysterious over human lives!!! I had a "General Biology" class today. Of course it was in in-understandable Japanese as always. It was talking about the various control of gene expression. Of course it was a useless lecture which tried to summarized the whole things in only a one and 15 minutes lecture. SO STUPID!!! I mean, how could it be happened??!! The whole process of the gene expression control is like one bible itself. As I expected, even the lecturer was overwhelmed with the whole lecture material, and just delivered us the title and subtitles written in the "Molecular Biology of the Cells" part II chapter 7... (ya!! You may open it by yourself)

But while I was fighting my sleepiness in the class, my eyes and ears caught a glimpse of DNA double breaks and HRR....!! What does it mean??!! Does it mean, I am a good student for starting reviewing it for the last 2 days??!!! I was so happy that I fought the whole forces to sleep in the class and tried as best as I could to listen the lecturer to the end.   

And!!! As I promised, following the previous post about DSBR, I continue the next discussion to the first strategy of DSBR: non homologous end-joining (NHEJ).

If HRR is known as the most assuring way, then NHEJ is more well-known as the most straightforward way to repair DSB. It simply rejoin the broken ends, regardless any genetic sequences at the break. OF COURSE, this pathway leads to alteration (or just say the changing) of the DNA sequences and mutation, which makes it considered as an error-prone. The following picture introduces us to the various factors involved in the pathway.

 

The basic explanation for the NHEJ pathway is as the next picture follows. The DNA breaks are recognized by the Ku70/80 complex. This recognition will promotes the recruitment of DNA-dependent kinase catalytic subunit (DNAPKcs). Afterward, it will induce the DNA end processing enzymes (in the form of kinase activity). This kinase activity will contributes to the phosphorylation of some histones and thus promotes the ligation process.   

However, not all broken DNA ends could immediately be ready for ligation. One or more of the ends might have an abnormal structure. Therefore, these abnormal ends need to be trimmed. In a low eukaryote cells such as yeast, the MRE11, Rad50, and NBS1 will make an M-R-N complex with endo- and exonucleolytic activities might share an important role in trimming these ends. However, in higher eukaryote cells, another nuclease named Artemis is recruited to the phosphorylated and activated DNA breaks by DNAPKcs. This nuclease will trim the overhang ends and prepare the DNA to be ligated by DNA ligase IV-XRCC4-XLF complex.  

That's it!! I hope I explained it quite simple to be understood!!

See you on the next post... I am studying the MMEJ right now... hope I could post it ASAP ^^

Thanks for reading, and of course, comments and discussion are highly welcomed!!