R5.4e: DNA Damage Response Genes

Homologous Recombination

MRN Complex (MRE11A, RAD50, NBN)

The MRN complex, also involved in sensing DNA damage, is is involved in cutting back a single strand on one side of the DSB.

Replication Protein A1, A2, A3 and A4 (RPA1, RPA2, RPA3, RPA4)

These four genes code for a components of replication protein A (RPA), which binds to exposed single strands of DNA to prevent linkage. This occurs directly after a single strand is exposed by the MRN complex.

Breast Cancer 1, Early Onset (BRCA1)

BRCA1 is recruited into a BRCA1 associated complex (which includes many of the sensors, such as ATM/ATR and the MRN complex). This appears to coordinate many of the activities in HR.

Breast Cancer 2, Early Onset (BRCA2)

BRCA2 is closely associated with HR, regulating the binding of RAD51 to single strands of DNA already coated with RPA.

X-Ray Repair Complementing Defective Repair in Chinese Hamster Cells 2 and 3 (XRCC2, XRCC3)

Rad51 Homolog B, C and D (RAD51B, RAD51C, RAD51D)

The products of these five genes associate during homologous recombination, forming kinases when located near single stranded DNA.

Rad51 Homolog (RAD51)

Interacts with BRCA1/2, coating single stranded DNA (ssDNA) by replacing RPA. ssDNA coated with RAD51 seeks out homologous DNA strands and allows HR to occur.

Bloom Syndrome, RecQ Helicase Like (BLM)

A member of the RecQ family of helicases, involved in separating the two annealed strands of DNA from the sister chromatid to allow HR to take place.

Topoisomerase (DNA) III Alpha (TOP3A)

Associates with BLM, and prevents strands of DNA from becoming twisted or developing knots. 

Non-Homologous End Joining (NHEJ)

X-Ray Repair Complementing Defective Repair in Chinese Hamster Cells 5 and 6 (XRCC5, XRCC6)

These sensors of DNA damage are also critical for NHEJ, coating both ends of the double strand break and attracting PRKDC to the site of damage.

Protein Kinase, DNA-activated, Catalytic Polypeptide (PRKDC)

As well as leading to activation of numerous transducer molecules, PRKDC also binds the two ends together to prevent dissociation. When phosphorylated by itself or other proteins, PRKDC alters its shape to allow other repair proteins access to the break sites.

DNA Cross-link repair 1C (DCLRE1C)

Also known as Artermis, DCLRE1C processes the ends of DNA so they are suitable for ligation.

Polynucleotide Kinase 3'-phosphatase (PNKP)

PNKP has a similar role to Artermis, processing incompatible ends so that they can be ligated later.

Polymerase (DNA-directed), Gamma and Lambda (POLG, POLL)

These related repair polymerases may add nucleotides to non-blunt ends of DNA to facilitate ligation.

Polymerase (DNA-directed), Mu (POLM)

Deoxynucleotidyltransferase, terminal (DNTT)

These may add extra bases to a blunt end of DNA prior to ligation.

Ligase IV, DNA, ATP-dependent (LIG4)

As the final step in NHEJ, LIG4 ligates the two strands of DNA together with the aid of XRCC4.

X-ray Repair Complementing Defective Repair in Chinese Hamster Cells 4 (XRCC4)

XRCC4 combines with LIG4 to enable ligation, the final step in NHEJ.