R5.4d: DNA Damage Response

There are set pathways which the cell uses to repair specific types of DNA damage.

Homologous Recombination (HR)

Homologous Recombination is the most accurate form of double strand break repair, for it uses the complementary sister chromatid as a template. This means that HR can only occur in a cycling cell that is in the latter parts of S phase, all of G2 phase, or in early M phase. Non cycling cells must use other methods (non-homologous end joining, below) to repair double strand breaks.
Homologous recombination is triggered by the attraction of the ATM/ATR protein and the MRE complex of proteins to the site of damage. ATM is involved in the signaling and activation of repair pathways, which causes a halt in the cell cycle as well as increasing production of repair molecules such as BRCA1, BRCA2 and RAD51.
Repair is started by the MRE complex, which removes several bases from a single strand on each side of the break. This exposes a single strand on each side of the break, which is subsequently coated by Replication Protein A (RPA; made up of four component proteins 1-4), preventing aberrant binding of the single strands. Replacement of RPA by RAD51 occurs under supervision from the BRCA complex. This leads to invasion of the sister chromatid by the damaged strand, and DNA polymerase uses the undamaged strand to replace the damaged region of each side of the original strand. The final step is the cutting of the crossover points.

Non-Homologous End Joining (NHEJ)

Non-homologous end joining is the other well understood pathway for double strand break repair. It can be used at any stage in the cell cycle, but is not as accurate as it does not use a template for repair. It is still a relatively accurate repair pathway, as it is responsible for DNA damage repair in most cells at some time (and we haven't turned into a puddle of goo yet).
NHEJ also starts with recognition of the strand break (by XRCC5 and XRCC6, which attract PRKDC) and signaling to the cell that damage has occured. PRKDC plays an important role in attracting repair proteins as well as preventing the ends from dissociating.
As a first step, each end of the double strand break must be 'processed', removing damaged bases and adding bases if necessary (this is where the error comes in). There are numerous genes involved, including DCLRE1C (Artermis) and PNKP which remove bases, and POLG and POLL polymerases which add bases.
The second step involves the ligation of the two ends; this is accomplished by LIG4 with assistance from XRCC4.

Base Excision Repair / Single Strand Break Repair (BER/SSBR)

Base excision repair and single strand break repair pathways are related. If a base is altered by any means, it causes an abnormality in the shape of the DNA helix; this can be detected by glycosylases which remove the damaged base. The sugar/phosphate backbone of the affected base is also removed by APE1, leaving a single strand break.
Single strand breaks are detected by PARP and the ends cleaned by PNK.
The end process of both methods is a gap in one strand of the DNA helix, which must be repaired.
Short patching is performed by POLB (polymerase beta), which inserts the correct base, and LIG3 which unites the strand.
Long patching is more complicated, involving the removal of a section of the DNA around the single break and reconstruction of the region by polymerases. LIG1 is involved in completing the repair.

Nucleotide Excision Repair (NER)

Nucleotide excision repair is carried out by an array of proteins. It is involved in the removal of bulky DNA lesions and crosslinks, which are not typical of ionising radiation. The damaged strand is detected, and incisions made up and downstream of the lesion. The entire section is removed (similar to long patch, above) and polymerases and ligases replace the strand.

Mismatch Repair (MMR)

Mismatch repair occurs during DNA replication, and ensures highly accurate translation of DNA. If an incorrect base is inserted by DNA polymerase, the MMR proteins are able to detect the incorrect shape of the DNA helix and excise the incorrect base. This allows repair of the lesion.