The dual nature of homologous recombination in plants

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Review TRENDS in Genetics Vol.21 No.3 March 2005 177Table 2. Plant mutants with altered somatic homologous recombination frequency a,bMutant c Gene (AGI Pathway Assay Repair and recombination phenotype Refsaccess number)Genetic screens for genotoxic stress sensitivityxrs4 ND ND X-ray sensitivity, genetic screen X-ray, MMS and MMC sensitivity; [30,31]decreased somatic HR and increasedmHRxrs9 ND ND X-ray sensitivity, genetic screen X-ray and MMS sensitivity; decreased [30,31]somatic HR and mHRxrs11 ND ND X-ray sensitivity, genetic screen X-ray and MMC sensitivity; defective in [30,31]X-ray-mediated somatic HR inductionHyrec d ND HR Spontaneous g-ray resistant, increased interhomologs[37]HR, intrachromosomal HRunchangedMim At5 g61460 Chromatin MMS sensitivity, genetic screen MMS, UV-C, MMC and X-ray sensitivity; [34,74]decreased somatic HRBru At3 g18730 ND MMS sensitivity, genetic screen MMS, MMC, UV-C and bleomycin [35]sensitivity; increased somatic HR, TGSreleaseGenetic screens for altered HR phenotypes using chromosomal HR substratesCentrin2 At4 g37010 NER Increased HR genetic screen UV-C sensitivity; increased somatic HR, [46]defective in repair of UV-damaged DNAino80 At3 g57300 HR Altered HR genetic screen Decreased somatic HR [47]Reverse genetics and functional genomicsrad50 At2 g31970 NHEJ Homology to known protein MMS sensitivity; sterility, telomeric [18,38,40]defect, increased somatic HRrad17 At5 g66130 Cell-cyclecheckpointHomology to known protein Bleomycin and MMC sensitivity;increased somatic HR, rapid DSB repairdefect[39]rad9 At3 g05480 Cell-cyclecheckpointHomology to known proteinBleomycin and MMC sensitivity;increased somatic HR, rapid DSB repairdefectercc1 At3 g05210 NER Homology to known protein UV-C sensitivity; ECR with nonhomologousoverhangs reduced, decreasedchromosomal HRsnm1 At3 g26680 HR? Functional genomics Bleomycin and H 2 O 2 sensitivity;impaired induction of HR by H 2 O 2 andflagellin but not bleomycin, MMC andMMSMutants previously isolated for other functionrad1 (uvh1,xpf)At5 g41150 NER Known UV-C-sensitive mutant UV-B, UV-C, g-ray and cisplatin sensitivity;ECR with nonhomologous overhangsreduced, impaired HR inductionby bleomycinuvr2 (phr1) At1 g12370 Photorepair Known UV-B-sensitive mutant UV-B sensitivity; defective in CPDsphotorepair, slightly increased somaticHRcim3 ND Plant defense Uncharacterized defense mutant Constitutively activated systemicacquired resistance, increased somaticHRvtc1 (soz1) At2 g39770 Vitamin C Known UV-B-sensitive mutant UV-B and H 2 O 2 sensitivity; ascorbicaciddeficient, increased somatic HRTt4 (chs) At5 g13930 Flavonoid Known UV-B-sensitive mutant UV-B sensitivity; chalcone synthasedeficient, increased somatic HRTt5 (chi) At3 g55120 Flavonoid Known UV-B-sensitive mutant UV-B sensitivity; chalcone isomerasedeficient, increased somatic HR[39][73][44][75–78,80][41,53,81][43][82,83], (G. Ries,PhD thesis,Basel University,1999)[82,84], (G. Ries,PhD thesis,Basel University,1999)[82,84], (G. Ries,PhD thesis,Basel University,1999)a Abbreviations: CPDs, cyclobutane pyrimidine dimers; ECR, extrachromosomal HR; HR, homologous recombination; mHR, meiotic HR; MMC, mitomycin C; MMS,methylmethane sulfonate; ND, not determined; NER, nucleotide excision repair; NHEJ, nonhomologous end-joining; TGS, transcriptional gene silencing.b Within the past few years, the use of various strategies proved to be successful and complementary in identifying a large number of mutants involved in somatic HR inplants. Such mutants are listed in the top part of the table with the expected impaired pathway and a summary of their phenotypes. These include: (i) mutants originatingfrom indirect genetic screens (i.e. by searching for mutations resulting in altered sensitivity to genotoxic stress and by subsequently testing their effect on HR); (ii) mutantsobtained through direct genetic screening of mutagenized Arabidopsis lines carrying a chromosomal HR reporter construct; (iii) mutants originating from reverse geneticapproaches (i.e. testing publicly available Arabidopsis mutants in genes homologous to recombination or repair genes known from other organisms) or genes inferred fromfunctional genomics studies; and (iv) some additional previously characterized mutants are listed in the lower part of the table. These were identified for other phenotypesand only subsequently shown to affect HR.c Alternative names are indicated in parenthesis.d Hyrec is in Nicotiana tabacum; all other mutants are in Arabidopsis thaliana.www.sciencedirect.com
178Review TRENDS in Genetics Vol.21 No.3 March 2005DSBChromatin eventsBRU ?INO80 ?MIM ?RAD50MRE11?ATMATRKU70KU80NHEJSignalingPathwaydetermination(ii) Strand invasionRAD51 ?(i) 5′- 3′ resectionRAD54L ?DSB repair modelSDSA modelInterconnectionwith other repairSNM1 pathways(vii) First strand invasionand synthesisCentrinRAD17RAD9(iii) New DNA synthesisBranch migration(viii) Second strand invasionand synthesis(iv) Holliday junctionresolutionRAD1ERCC1(ix) New strands annealingand synthesis(x) Gene conversion withunaffected template(v) No crossing-over(vi) Crossing-over offlanking markersTRENDS in GeneticsFigure 2. The DSB and synthesis-dependent strand-annealing (SDSA) repair models of HR in plants. (i–vi) DSB repair model for HR. (i) Initially the DSB is resected in 5 0 -to-3 0direction, producing 3 0 single-stranded DNA ends. (ii) The 3 0 ends invade a homologous DNA duplex forming a DNA crossover, or Holliday junction (HJ), and providingprimers to initiate new DNA synthesis. (iii) The region of heteroduplex is extended through branch migration of the HJ away from the initial crossover site. (iv) HJs areresolved by cleavage of either the crossed (green arrows) or the non-crossed (black arrows) strands of the junction. Resolution in the same orientation does not affect theflanking markers (v), whereas a mixed resolution of the two HJs does (vi). (vii–x) The SDSA model for HR. (vii) One of the 3 0 single-stranded tails invades the homologousduplex, priming DNA synthesis. (viii) The other 3 0 single-stranded tail can also subsequently invade the homologous duplex and prime synthesis. After displacement from thedonor duplex (ix) the nascent strand pairs with the other 3 0 single-stranded tail and DNA synthesis and ligation complete repair (x). Factors known to be involved in HR inplants, most of which are discussed in the main text, are depicted.Recently, the combination of various approaches toisolate mutants in somatic HR has led to a dramaticincrease in our knowledge about plant HR, its pathways,its components and its regulation (Table 2 and Figure 2).Plant mutants screened for sensitivity to UV, methylmethanesulfonate (MMS) and X-rays were tested forHR; publicly available random insertional mutants ingenes known from other organisms to be involved in HRand in genes inferred from functional genomic approacheswere analyzed. Finally, direct screens for altered levelsof HR in populations of mutagenized recombinationtester-lines were conducted. All approaches yielded HRmutants, and proved to be complementary (Table 2).Strikingly, genetic screen approaches yielded many novelgenes or genes not expected to be involved in theregulation of HR.Some of the X-ray-sensitive mutants were found to bechanged at the level of somatic recombination, some atthe level of mHR and some at both levels (xrs mutants inTable 2). The screens for MMS sensitivity yielded the twomutants mim [34] and bru [35]. The MIM gene encodes aprotein closely related to the structural maintenance ofchromosomes (SMC) family of proteins, which have acentral role in chromosome organization and dynamics inbudding yeast. The yeast MIM homolog, Smc6, hasrecently been implicated in interchromosomal and sisterchromatidrecombination [36]. In the bru mutant, inwhich the stability of heterochromatin is affected, levels ofsomatic HR are increased. It is therefore entirely possiblethat the elevated HR levels in bru plants reflect anincreased sensitivity to DNA-damaging agents or animproved accessibility to the sites of damage for repairfactors rather than a direct involvement in the repairmachinery. It is of interest to mention the only describedhyper-recombinogenic mutant isolated in a non-Arabidopsisspecies: a tobacco mutant obtained in a transposonwww.sciencedirect.com
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The dual nature of homologous recombination in plants

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