Question

GENETIC

Are there cellular mechanisms to repair chromosomal level errors, such as those that cause translocations and inversions? Explain.

Answer 1

Every day more than 1 million incidents causing molecular damage occur per cell per day. It may cause structural damage or impair a cells ability to transcribe the right mRNA. It may also change somekey nuclear bases which may eventually cause cell death. As a result, DNA repair mechanisms have evolved that counter such threats.

DNA repair mechanisms can be of the following types -

1. Single strand damage repair : When only one of the cell gets damaged, the undamaged strand can act as a template to guide the damaged strands repair. It can be done in the following ways.

• Mismatch repair -It is used to correct errors that cannot be repaired by proofreading. Mut class proteins are involved in this repair. One protein identifies the mismatch and another employs the endonuclease to cleave the damaged region of DNA.
• Nucleotide excision repair - Repairs damages like pyrimidine dimerisation and other damage that distort the helical shape of the DNA. 12 to 24 bp long strands are removed and replaced with a correct new strand. This process is very conserved across both prokaryotes and eukaryotes.
• Base Excision repair - Single damaged base pairs are removed by recruiting glycosylases. AP endonucleases nick the damaged DNA backbone at the same site. The new strand is synthesized according to the complementary template.

2. Repair by Direct Reversal - DNA can eliminate damage by chemically reversing it. No template is required. In the case of pyrimidine dimerisation, an enzyme photolyase is recruited to undo the damage. In case of methylation, the enzyme methyl guanine methyl transferase is employed to repair the damage.

3. Double Strand Breaks - Sometimes both the strands of the helix can break due to damage. DNA Ligase IV forms a complex with the cofactor XRCC4 and directly joins the two ends. To guide accurate repair small nucleotide sequences called microhomologies present on the single stranded tails of DNA are relied upon.