description
Homology directed repair (HDR) through homologous recombination (HRR) or single strand annealing (SSA) requires extensive resection of DNA double strand break (DSB) ends (Thompson and Limoli 2003, Ciccia and Elledge 2010). The resection is performed in a two-step process, where the MRN complex (MRE11A:RAD50:NBN) and RBBP8 (CtIP) bound to BRCA1 initiate the resection. This step is regulated by the complex of CDK2 and CCNA (cyclin A), ensuring the initiation of HRR during S and G2 phases of the cell cycle, when sister chromatids are available. The initial resection is also regulated by ATM-mediated phosphorylation of RBBP8 and CHEK2-mediated phosphorylation of BRCA1 (Chen et al. 2008, Yun and Hiom 2009, Buis et al. 2012, Wang et al. 2013, Davies et al. 2015, Parameswaran et al. 2015). After the initial resection, DNA nucleases EXO1 and/or DNA2 perform long-range resection, which is facilitated by DNA helicases BLM or WRN, as well as BRIP1 (BACH1) (Chen et al. 2008, Nimonkar et al. 2011, Sturzenegger et al. 2014, Suhasini et al. 2011). The resulting long 3'-ssDNA overhangs are coated by the RPA heterotrimers (RPA1:RPA2:RPA3), which recruit ATR:ATRIP complexes to DNA DSBs and, in collaboration with RAD17:RFC and RAD9:HUS1:RAD1 complexes, and TOPBP1 and RHNO1, activate ATR signaling. Activated ATR phosphorylates RPA2 and activates CHEK1 (Cotta-Ramusino et al. 2011), both of which are necessary prerequisites for the subsequent steps in HRR and SSA

external resources
NCBI:1309101
REACTOME:R-HSA-5693607
PUBMED:25122754
PUBMED:18171670
PUBMED:20965415
PUBMED:22231403
PUBMED:25558984
PUBMED:19357644
PUBMED:21325134
PUBMED:21240188
PUBMED:21659603
PUBMED:23468639
PUBMED:25659039

genes
ATM , ATR , BARD1 , BLM , BRCA1 , CCNA2 , CDK2 , CHEK1 , DNA2 , H2AFX , HIST1H2BD , HIST1H2BB , HUS1 , MRE11 , NBN , PPP4C , RAD1 , RAD9A , RAD17 , RBBP8 , RFC2 , RFC3 , RFC4 , RFC5 , RNF4 , RPA1 , RPA2 , RPA3 , RPS27A , SUMO2 , TOP3A , TP53BP1 , UBA52 , UBB , UBC , UBE2I , UBE2N , UBE2V2 , SUMO1 , NSD2 , WRN , HIST3H3 , HIST1H4I , HIST1H2BG , HIST1H2BL , HIST1H2BN , HIST1H2BM , HIST1H2BF , HIST1H2BE , HIST1H2BH , HIST1H2BI , HIST1H2BC , HIST1H2BO , HIST2H2BE , HIST1H4A , HIST1H4D , HIST1H4F , HIST1H4K , HIST1H4J , HIST1H4C , HIST1H4H , HIST1H4B , HIST1H4E , HIST1H4L , HIST2H4A , CCNA1 , TIMELESS , HERC2 , HIST1H2BJ , RNF8 , EXO1 , BABAM2 , MDC1 , RAD50 , KAT5 , TOPBP1 , BABAM1 , SIRT6 , PIAS4 , UIMC1 , TIPIN , CLSPN , BRCC3 , RMI1 , RHNO1 , BRIP1 , ATRIP , ABRAXAS1 , HIST1H2BK , RMI2 , HIST4H4 , HIST3H2BB , RAD9B , PPP4R2 , RNF168 , HIST1H2BA , HIST2H4B , MIR4741 ,