Types of Repair Mechanisms That Combat DNA Damage
Repair mechanisms recognize and manage DNA error caused by spontaneous or induced mutations on the molecular level.
Direct reversal repairs DNA base damage caused by ultraviolet light (UV). UV light damages a cyclobutane pyrmidine dimer, and the enzyme CPD photolyase repairs direct replacement of base damage. The enzyme splits the photodimer to regenerate the original bases. This is called photoreactivation due to requirement of light for function.
Base-excision repair targets nonbulky damage to bases through removal of the incorrect or damaged bases. DNA glycosylases are the primary family of enzymes in base-excision repair. They cleave base-sugar bonds to create apyrmidinic (AP) sites. AP endonuclease nicks the damaged strand upstream of the AP site. dRpase (deoxyribophosphodiesterase) removes a stretch of the neighboring sugar-phosphate residues to allow DNA polymerase to fill the gap with nucleotides complementary to the other strand. DNA ligase seals the nick created by AP endonuclease.
Nucleotide excision repair (NER) involves multiple proteins binding at the site of DNA damage caused by UV light, to repair the base damage. This complex process includes recognition of damaged base, assembly of multiprotein complex at the site, cutting the damaged strand several nucleotides upstream and downstream of the damage site and removal of the nucleotides, and use of the undamaged strand as a template for DNA polymerase followed by strand ligation (574). Two pathways of nucleotide-excision repair include global genomic repair (GGR) and transcription-coupled NER. In GGR, a stalled replication fork is recognized and TFIIH is recruited to induce incision of damaged strand by a multiprotein complex, then bypass polymerase synthesizes new DNA strand and ligase 1 seals the DNA strand.
Post replication repair: Mismatch Repair
Mismatch repair targets mismatched bases and loops caused by insertion and deletion of nucleotides during replication. The pathway first recognized mismatched base pairs, determines which base in the mismatch is the incorrect one, ultimately resulting in the excision of the incorrect base and repair synthesis. The MutS protein recognizes mismatched bases; MutH recognizes methylated parent strand and nicks daughter strand; and UrvD protein binds the nick and uses helicase activity to unwind the nick. Any dysfunction or lack of mismatch repair genes leads to cancer.
Error-prone repair: translesion DNA synthesis
Not all DNA repair mechanisms are completely efficient to replace or repair the DNA damage. The SOS system bypasses DNA damage and the DNA damage remains in the strand. In this process, polymerase III recognizes the DNA damage and stalls at the site. Polymerase V acts as a bypass polymerase and replaces polymerase III and continues DNA synthesis passive over the DNA damage.
Introduction to Genetic Analysis by Sean B. Carroll, John Doebley, Anthony J.F. Griffiths, and Susan R. Wessler