Table 2.
Role of Factors in homologous recombination or inter-strand cross link repair versus replication fork protection.
Factor | In DNA repair | In fork protection | References |
---|---|---|---|
ATR | Promote long range resection | Promote ‘rewired’ fork protection | [105]. |
BLM | Promote end resection, Holliday junction dissolution and RAD51 dissociation during late HR | Promote RAD51 dissociation | [71,72,78,129,130,132]. |
BRCA1-BARD1 | Counteract 53BP1-Shieldin and promote PALB2-BRCA2 and RAD51 recruitment | Promote RAD51 recruitment by PIN1 | [79,102,103]. |
BRCA2 | Stabilise RAD51 | Stabilise RAD51 | [9,79,80,102]. |
CtIP | Initiate MRE11-mediated resection | Restrict fork reversal/protect reversed forks and aid MRE11-mediated degradation | [61,62,63]. |
DNA2 | Extend MRE11 resection | Resect ‘wild-type’ and de-protected forks | [8,66,69,70,71,73,161]. |
EXD2 | Promote MRE11 resection | Suppress fork reversal | [56,57,58,59]. |
EXO1 | Extend MRE11 resection | Extend MRE11 resection | [62,161]. |
FANCD2 | Histone mobilisation for ICL repair, recruitment of FAN1 nuclease | Histone mobilisation, increase TLS, direct RAD51 stabilisation | [72,84,116,162]. |
FBH1 | Dissociate RAD51 filaments | Promote fork reversal, promote RAD51 dissociation | [10,41,67]. |
MRE11 | Initiate short-range resection | Resect unprotected forks, promote fork restart | [9,15,18,40,59,62,65,66,67,77,78,79,80,81,82,83,84]. |
PALB2 | Promote BRCA2 recruitment via BRCA1 | BRCA1-independent recruitment of BRCA2 | [103,104,105]. |
PARP | Break excision repair, Pol-theta mediated end joining | Inhibit fork restoration, recruit MRE11, inhibits fork restoration, RAD51 stabilisation | [53,86,141,163]. |
PDS5 | Promote BRCA2 recruitment | Promote BRCA2 recruitment | [77,112]. |
RAD51 | Strand exchange | Promote fork reversal, protect forks from degradation | [2,8,9,10,15,48,49,79,80,93,94,95]. |
RAD51 paralogs | Stabilise RAD51 | Promote RAD51 recruitment | [82,124]. |
RAD52 | Promote RAD51 loading, single strand annealing, break-induced-repair | Suppress SMARCAL1 recruitment, promote MRE11 recruitment | [9,23,24]. |
RECQL5 | Dissociate RAD51 filaments | Protect against degradation | [78,133]. |
RIF1-PP1 | Part of the Shieldin complex that promotes NHEJ and inhibits DNA resection | Inhibit DNA2/WRN | [69,70]. |
RNF168 | Recruit 53BP1 | Restrict fork reversal | [65,164,165]. |
SLX4 | Scaffold for nucleases in Holliday Junction cleavage | Scaffold for nucleases involved in fork cleavage | [66,67]. |
WRN | Support DNA2 in long-range resection | Support DNA2 (helicase), prevent MRE11-dependent degradation (exonuclease) | [8,40]. |