Q: that bypass proofreading. This repair systemQ: that bypass proofreading. This repair system

Q: Mutation
could be caused by either copying errors or environmental factors, was
wondering if damage on DNA could be reversed or repaired.

 

Figure 1: The 3 major forms of DNA
repair (Arnaud, 2015).

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DNA integrity
is often compromised by environmental agents like UV ray. If these damages are
not repaired, it could often lead to mutation or diseases. One good example is
environmental-induced DNA damage such as skin cancer and oxidative damage
induced by metabolic by-products such as free radicals (Narendhirakannan and
Hannah, 2012).

Fortunately,
these damages are often detectable and can be repaired in both prokaryotic and
eukaryotic organisms. Given the fact that DNA is an essential molecule in cell
cycle, numerous checkpoint mechanisms were put in place to ensure that the DNA
molecules are intact before the commencement of DNA replication and cell
division. Upon detection, specific DNA repair molecule binds directly on the
site of damage or around the affected site, promoting the formation of complex
that initiate the repair.

In cases where
there are single strand damage, excision repair mechanisms are initiated to remove
the damage nucleotide and replace it with the correct nucleotide complimentary
to the template strand. One of such repair is called base excision repair
(BER). BER uses enzymes known as glycosylases to remove the affected
nucleotide. This results in the creation of an apurinic site. Another enzyme
called AP endonucleases nick the damaged DNA backbone around the AP site. DNA
polymerase removes the damaged section through 5′ to 3′ exonuclease activity
and initiate a correct synthesis of a new strand by using the template strand
as a guide. Another method called nucleotide excision repair (NER) targets helix-distorting
damages like pyrimidine dimerization. Damaged regions have up to 24 nucleotides
removed through a systematic step of recognition of damages, excision of
damaged DNA both upstream and downstream of damage by endonucleases and the
resynthesising of affected DNA region. Lastly, mismatch repair system found in
all cells act as a last checkpoint that stop errors that bypass proofreading.

This repair system uses 2 key proteins: one that detects the mismatch and one
that induce endonuclease to cleave the newly formed DNA strand near the damage
site (Chatterjee and Walker, 2017).

 

 

Figure 2: Studies have shown that NHEJ-deficiency
mouse have less effective repair mechanism (MacDonald, 2018)

In recent
studies, accumulation of mutations have shown to impair repair mechanisms,
resulting in deregulation of transcription patterns and reduced fitness. In a
research done on mice with deficiency in Non-homologous end joining (NHEJ) are
prone to infection and lymphoma. NHEJ is one of the major repair mechanism that
repair double-strand breaks and is known to decline in organisms and animal
overtime due to the limitation of Ku. Ku is known to induce recruitment of
Artemis-DNA-PCKcs complex that is essential to the ligation of double strand
breaks (Gorbunova et al., 2007).

 

References

Narendhirakannan,
R. and Hannah, M. (2012). Oxidative Stress and Skin Cancer: An Overview. Indian
Journal of Clinical Biochemistry, 28(2), pp.110-115.

Chatterjee, N.

and Walker, G. (2017). Mechanisms of DNA damage, repair, and mutagenesis.

Environmental and Molecular Mutagenesis, 58(5), pp.235-263.

Gorbunova, V.,
Seluanov, A., Mao, Z. and Hine, C. (2007). Changes in DNA repair during aging.

Nucleic Acids Research, 35(22), pp.7466-7474.

MacDonald, F.

(2018). It’s Happening: Scientists Can Now Reverse DNA Ageing in Mice. online
ScienceAlert. Available at:
https://www.sciencealert.com/scientists-have-successfully-reversed-dna-ageing-in-mice
Accessed 6 Jan. 2018.

Arnaud, C. (2015).

Tomas Lindahl, Paul Modrich, And Aziz Sancar Win 2015 Nobel Prize In Chemistry
For DNA Repair | October 12, 2015 Issue – Vol. 93 Issue 40 | Chemical &
Engineering News. online Cen.acs.org. Available at:
https://cen.acs.org/articles/93/i40/Tomas-Lindahl-Paul-Modrich-Aziz.html
Accessed 6 Jan. 2018.