122:
1241:
239:(Proliferating Cell Nuclear Antigen). PCNA forms typical patterns in the nucleus of the cell through which the current cell cycle can be determined. The polymerase synthesizes the missing part of the broken strand. When the broken strand is rebuilt, both strands need to uncouple again. Multiple ways of "uncoupling" have been suggested, but evidence is not yet sufficient to choose between models (
25:
176:. HDR maintains genomic stability by repairing broken DNA strands; it is assumed to be error free because of the use of a template. When a double strand DNA lesion is repaired by NHEJ there is no validating DNA template present so it may result in a novel DNA strand formation with loss of information. A different
222:
are removed and single strand overhangs are formed. Meanwhile, from the beginning, every piece of single stranded DNA is covered by the protein RPA (Replication
Protein A). The function of RPA is likely to keep the single stranded DNA pieces stable until the complementary piece is resynthesized by a
184:
expressed in the cell. This protein error may cause processes in the cell to fail. For example, a receptor of the cell that can receive a signal to stop dividing may malfunction, so the cell ignores the signal and keeps dividing and can form a cancer. The importance of HDR can be seen from the fact
217:
component for attracting proteins to the damaged location. Several research groups have suggested that the phosphorylation of H2AX is done by ATM and ATR in cooperation with MDC1. It has been suggested that before or while H2AX is involved with the repair pathway, the MRN complex (which consists of
328:
including double-strand breaks. However, the oocytes can efficiently repair DNA double-strand breaks, allowing the restoration of genetic integrity and the protection of offspring health. The process by which oocyte DNA damage can be corrected is referred to as homology directed
263:
homology directed repair is primarily a response to spontaneous or induced damage that occurs during vegetative growth. (Also reviewed in
Bernstein and Bernstein, pp 220–221). In order for yeast cells to undergo homology directed repair there must be present in the same
292:. Evidence indicates that, due to the special nearby relationship they share, sister chromatids are not only preferred over distant homologous chromatids as substrates for recombinational repair, but have the capacity to repair more DNA damage than do homologs.
218:
Mre11, Rad50 and NBS1) is attracted to the broken DNA ends and other MRN complexes to keep the broken ends together. This action by the MRN complex may prevent chromosomal breaks. At some later point the DNA ends are processed so that unnecessary residuals of
213:(noted as γH2AX) is phosphorylated within seconds after damage occurs. H2AX is phosphorylated throughout the area surrounding the damage, not only precisely at the break. Therefore, it has been suggested that γH2AX functions as an
246:
The co-localization of Rad51 with the damage indicates that HDR has been initiated instead of NHEJ. In contrast, the presence of a Ku complex (Ku70 and Ku80) indicates that NHEJ has been initiated instead of HDR.
250:
HDR and NHEJ repair double strand breaks. Other mechanisms such as NER (Nucleotide
Excision Repair), BER (Base Excision Repair) and MMR recognise lesions and replace them via single strand perturbation.
235:(Breast Cancer Associated), Rad51 couples a complementary DNA piece which invades the broken DNA strand to form a template for the polymerase. The polymerase is held onto the DNA strand by
156:. Other examples of homology-directed repair include single-strand annealing and breakage-induced replication. When the homologous DNA is absent, another process called
470:
Bolderson, Emma; Richard, Derek J.; Zhou, Bin-Bing S. (2009). "Recent
Advances in Cancer Therapy Targeting Proteins Involved in DNA Double-Strand Break Repair".
121:
42:
1174:
1148:
304:. The remaining two-thirds, or more, of homology directed repair occurs as a result of interaction between non-sister homologous chromatids.
573:
809:
864:
89:
1117:
1048:
61:
108:
324:. In mammalian females the period of arrest may last for years. During this period of arrest, oocytes are subject to spontaneous
1132:
325:
288:. However, in the G2 stage of the cell cycle (following DNA replication), a second homologous DNA molecule is also present: the
68:
563:
312:
The fertility of females and the health of potential offspring critically depend on an adequate availability of high quality
209:). However, a number of experimental results point to the validity of certain models. It is generally accepted that histone
46:
75:
1107:
1014:
57:
640:"Frequent and efficient use of the sister chromatid for DNA double-strand break repair during budding yeast meiosis"
591:"Sister chromatids are preferred over homologs as substrates for recombinational repair in Saccharomyces cerevisiae"
1036:
860:
853:
694:"Oocytes can efficiently repair DNA double-strand breaks to restore genetic integrity and protect offspring health"
157:
953:
802:
342:
330:
145:
515:"Mechanisms of Rad52-independent spontaneous and UV-induced mitotic recombination in Saccharomyces cerevisiae"
35:
1143:
1053:
848:
148:. The HDR mechanism can only be used by the cell when there is a homologous piece of DNA present in the
909:
285:
269:
82:
834:
1265:
1244:
931:
795:
495:
423:"DNA repair in mammalian cells: DNA double-strand break repair: how to fix a broken relationship"
1127:
776:
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620:
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403:
385:
301:
289:
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843:
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771:
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615:
590:
539:
514:
398:
363:
219:
137:
1259:
1155:
976:
499:
300:
During meiosis up to one-third of all homology directed repair events occur between
1122:
1091:
1041:
1024:
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924:
265:
149:
483:
762:
656:
606:
530:
24:
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879:
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224:
177:
153:
389:
709:
186:
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624:
231:
replaces RPA and forms filaments on the DNA strand. Working together with
1139:
214:
190:
1086:
838:
321:
181:
125:
Double-strand break repair models that act via homologous recombination
1211:
966:
919:
914:
313:
273:
173:
1226:
1221:
1216:
1206:
1199:
1194:
1189:
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1164:
1019:
983:
904:
899:
894:
884:
692:
Stringer JM, Winship A, Zerafa N, Wakefield M, Hutt K (May 2020).
317:
232:
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210:
194:
120:
1112:
1068:
1063:
998:
993:
988:
961:
941:
936:
889:
236:
161:
791:
874:
869:
141:
18:
787:
747:"DNA double-strand break repair pathway choice and cancer"
243:). After the strands are separated the process is done.
205:
The pathway of HDR has not been totally elucidated yet (
421:
Pardo, B; Gomez-Gonzales, B; Aguilera, A (March 2009).
362:
Malzahn, Aimee; Lowder, Levi; Qi, Yiping (2017-04-24).
189:. The HDR mechanism has also been found in more simple
1100:
1079:
1007:
952:
825:
49:. Unsourced material may be challenged and removed.
180:sequence in the DNA strand results in a different
172:HDR is important for suppressing the formation of
513:Coïc E, Feldman T, Landman AS, Haber JE (2008).
284:, such a molecule is present in the form of the
687:
685:
803:
8:
364:"Plant genome editing with TALEN and CRISPR"
745:Aparicio T, Baer R, Gautier J (July 2014).
185:that the mechanism is conserved throughout
810:
796:
788:
268:a second DNA molecule containing sequence
770:
717:
665:
655:
614:
538:
446:
397:
379:
316:. Oocytes are largely maintained in the
109:Learn how and when to remove this message
144:lesions. The most common form of HDR is
354:
272:with the region to be repaired. In a
7:
427:Cellular and Molecular Life Sciences
47:adding citations to reliable sources
1118:Proliferating Cell Nuclear Antigen
1049:Microhomology-mediated end joining
152:, mostly in G2 and S phase of the
14:
1240:
1239:
1133:Meiotic recombination checkpoint
562:Luisa, Bozzano G. (2012-12-02).
23:
16:Mechanism of DNA repair in cells
34:needs additional citations for
638:Goldfarb T, Lichten M (2010).
589:Kadyk LC, Hartwell LH (1992).
1:
484:10.1158/1078-0432.CCR-09-0096
1015:Transcription-coupled repair
763:10.1016/j.dnarep.2014.03.014
657:10.1371/journal.pbio.1000520
531:10.1534/genetics.108.087189
1282:
1037:Non-homologous end joining
861:Nucleotide excision repair
854:Poly ADP ribose polymerase
607:10.1093/genetics/132.2.387
565:Aging, Sex, and DNA Repair
158:non-homologous end joining
58:"Homology directed repair"
1235:
439:10.1007/s00018-009-8740-3
381:10.1186/s13578-017-0148-4
1032:Homology directed repair
954:Homologous recombination
698:Proc Natl Acad Sci U S A
472:Clinical Cancer Research
343:Homologous recombination
331:homologous recombination
261:Saccharomyces cerevisiae
146:homologous recombination
140:to repair double-strand
130:Homology-directed repair
710:10.1073/pnas.2001124117
322:meiotic prophase arrest
164:) takes place instead.
1054:Postreplication repair
849:Uracil-DNA glycosylase
126:
368:Cell & Bioscience
286:homologous chromosome
259:In the budding yeast
124:
1160:core protein complex
835:Base excision repair
136:) is a mechanism in
43:improve this article
932:DNA mismatch repair
568:. Academic Press.
201:Biological pathway
168:Cancer suppression
127:
1253:
1252:
1128:Adaptive response
751:DNA Repair (Amst)
575:978-0-323-13877-2
478:(20): 6314–6320.
302:sister chromatids
119:
118:
111:
93:
1273:
1243:
1242:
812:
805:
798:
789:
784:
774:
732:
731:
721:
704:(21): 11513–22.
689:
680:
679:
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650:(10): e1000520.
635:
629:
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580:
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553:
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510:
504:
503:
467:
461:
460:
450:
433:(6): 1039–1056.
418:
412:
411:
401:
383:
359:
290:sister chromatid
114:
107:
103:
100:
94:
92:
51:
27:
19:
1281:
1280:
1276:
1275:
1274:
1272:
1271:
1270:
1256:
1255:
1254:
1249:
1231:
1101:Other/ungrouped
1096:
1075:
1003:
948:
844:DNA glycosylase
827:Excision repair
821:
816:
744:
741:
739:Further reading
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735:
691:
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469:
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339:
310:
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257:
220:chemical groups
203:
170:
115:
104:
98:
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52:
50:
40:
28:
17:
12:
11:
5:
1279:
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1056:
1051:
1046:
1045:
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1029:
1028:
1027:
1022:
1011:
1009:
1008:Other pathways
1005:
1004:
1002:
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996:
991:
986:
981:
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956:
950:
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831:
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792:
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785:
740:
737:
734:
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681:
630:
601:(2): 387–402.
581:
574:
554:
525:(1): 199–211.
505:
462:
413:
353:
352:
350:
347:
346:
345:
338:
335:
320:in a state of
309:
306:
297:
294:
256:
253:
227:. After this,
202:
199:
169:
166:
117:
116:
31:
29:
22:
15:
13:
10:
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6:
4:
3:
2:
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1181:
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1163:
1162:
1161:
1157:
1156:FANC proteins
1154:
1153:
1150:
1147:
1145:
1141:
1138:
1137:
1134:
1131:
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1038:
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1026:
1023:
1021:
1018:
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1016:
1013:
1012:
1010:
1006:
1000:
997:
995:
992:
990:
987:
985:
982:
978:
977:RecQ helicase
975:
974:
973:
970:
968:
965:
963:
960:
959:
957:
955:
951:
943:
940:
938:
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729:
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102:
99:November 2014
91:
88:
84:
81:
77:
74:
70:
67:
63:
60: –
59:
55:
54:Find sources:
48:
44:
38:
37:
32:This article
30:
26:
21:
20:
1159:
1140:DNA helicase
1123:8-Oxoguanine
1092:SOS response
1031:
972:RecF pathway
925:Excinuclease
754:
750:
701:
697:
647:
644:PLOS Biology
643:
633:
598:
594:
584:
564:
557:
522:
518:
508:
475:
471:
465:
430:
426:
416:
371:
367:
357:
311:
299:
274:diploid cell
260:
258:
249:
245:
240:
206:
204:
171:
133:
129:
128:
105:
96:
86:
79:
72:
65:
53:
41:Please help
36:verification
33:
1266:DNA repair
1080:Regulation
1059:Photolyase
819:DNA repair
757:: 169–75.
349:References
326:DNA damage
282:cell cycle
241:March 2008
225:polymerase
207:March 2008
193:, such as
178:nucleotide
154:cell cycle
69:newspapers
900:XPG/ERCC5
885:XPD/ERCC2
390:2045-3701
374:(1): 21.
191:organisms
187:evolution
1260:Category
1245:Category
895:XPF/DDB1
890:XPE/DDB1
781:24746645
728:32381741
676:20976044
595:Genetics
549:18458103
519:Genetics
500:14249728
492:19808869
457:19153654
448:11131446
408:28451378
337:See also
333:repair.
278:G1 phase
270:homology
215:adhesive
1087:SOS box
839:AP site
772:4051845
719:7260990
667:2957403
625:1427035
616:1205144
540:2390599
399:5404292
318:ovaries
314:oocytes
308:Oocytes
296:Meiosis
280:of the
266:nucleus
255:Mitosis
182:protein
150:nucleus
83:scholar
1212:FANCD2
1207:FANCD1
967:RecBCD
920:RAD23B
915:RAD23A
779:
769:
726:
716:
674:
664:
623:
613:
572:
547:
537:
498:
490:
455:
445:
406:
396:
388:
174:cancer
85:
78:
71:
64:
56:
1227:FANCN
1222:FANCJ
1217:FANCI
1200:FANCM
1195:FANCL
1190:FANCG
1185:FANCF
1180:FANCE
1175:FANCC
1170:FANCB
1165:FANCA
1025:ERCC8
1020:ERCC6
984:RAD51
905:ERCC1
496:S2CID
233:BRCA2
229:Rad51
195:yeast
138:cells
90:JSTOR
76:books
1113:PcrA
1069:CRY2
1064:CRY1
999:LexA
994:Slx4
989:Sgs1
962:RecA
942:MSH2
937:MLH1
865:ERCC
777:PMID
724:PMID
672:PMID
621:PMID
570:ISBN
545:PMID
488:PMID
453:PMID
404:PMID
386:ISSN
237:PCNA
211:H2AX
162:NHEJ
62:news
1149:WRN
1144:BLM
1108:Ogt
910:RPA
880:XPC
875:XPB
870:XPA
767:PMC
759:doi
714:PMC
706:doi
702:117
662:PMC
652:doi
611:PMC
603:doi
599:132
535:PMC
527:doi
523:179
480:doi
443:PMC
435:doi
394:PMC
376:doi
276:in
142:DNA
134:HDR
45:by
1262::
1158::
1142::
1042:Ku
775:.
765:.
755:19
753:.
749:.
722:.
712:.
700:.
696:.
684:^
670:.
660:.
646:.
642:.
619:.
609:.
597:.
593:.
543:.
533:.
521:.
517:.
494:.
486:.
476:15
474:.
451:.
441:.
431:66
429:.
425:.
402:.
392:.
384:.
370:.
366:.
197:.
863:/
837:/
811:e
804:t
797:v
783:.
761::
730:.
708::
678:.
654::
648:8
627:.
605::
578:.
551:.
529::
502:.
482::
459:.
437::
410:.
378::
372:7
160:(
132:(
112:)
106:(
101:)
97:(
87:·
80:·
73:·
66:·
39:.
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