LIG3 ligates remaining SSBs in MMEJ

Stable Identifier
R-HSA-5687675
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

The complex of DNA ligase 3 (LIG3) and XRCC1 is necessary for the completion of microhomology-mediated end joining (MMEJ), although DNA ligase 1 (LIG1) may also be involved (Sharma et al. 2015). LIG3:XRCC1 is recruited to MMEJ sites by the MRN complex and ligates single strand nicks that remain after reparative DNA synthesis by DNA polymerase theta (POLQ) at DNA double strand break (DSB) sites (Della-Maria et al. 2011). The annealing of microhomology regions between two 3'-ssDNA overhangs of resected DNA DSBs during MMEJ leads to deletion of the intervening DNA sequence and one of the microhomology regions in repaired double strand DNA (dsDNA) (Ghezraoui et al. 2014). In addition, as POLQ is error-prone, repaired DNA contains base substitutions (Ceccaldi et al. 2015). Similar to nonhomologous end joining (NHEJ), MMEJ (also known as alternative-NHEJ) can also produce translocations by joining unrelated DNA molecules (Ghezraoui et al. 2014).

Literature References
PubMed ID Title Journal Year
25201414 Chromosomal translocations in human cells are generated by canonical nonhomologous end-joining

Ghezraoui, H, Piganeau, M, Renouf, B, Renaud, JB, Sallmyr, A, Ruis, B, Oh, S, Tomkinson, AE, Hendrickson, EA, Giovannangeli, C, Jasin, M, Brunet, E

Mol. Cell 2014
25789972 Homology and enzymatic requirements of microhomology-dependent alternative end joining

Sharma, S, Javadekar, SM, Pandey, M, Srivastava, M, Kumari, R, Raghavan, SC

Cell Death Dis 2015
21816818 Human Mre11/human Rad50/Nbs1 and DNA ligase IIIalpha/XRCC1 protein complexes act together in an alternative nonhomologous end joining pathway

Della-Maria, J, Zhou, Y, Tsai, MS, Kuhnlein, J, Carney, JP, Paull, TT, Tomkinson, AE

J. Biol. Chem. 2011
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
DNA ligase activity of Extended microhomologous 3'-ssDNA overhangs-DSB:MRN:RBBP8:LIG3:XRCC1 [nucleoplasm]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed