The Yeast <i>HRS1</i> Gene Encodes a Polyglutamine-Rich Nuclear Protein Required for Spontaneous and <i>hpr1</i>-Induced Deletions Between Direct Repeats

Santos‐Rosa, Helena; Clever, Beate; Heyer, Wolf Dietrich; Aguilera, Andrés

doi:10.1093/genetics/142.3.705

Cited by 28 publications

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“…These data suggest that HPR1 participates in both transcription and recombination between repeats. This is supported further by the observations that mutations in different transcription factors suppress either the hyper‐recombination (Piruat and Aguilera, 1996; Santos‐Rosa et al ., 1996) or the ts phenotypes (Fan et al ., 1996; Uemura et al ., 1996) of hpr1Δ and that hpr1Δ ‐dependent deletions between GAL10 repeats are stimulated under conditions of activation of transcription (Fan et al ., 1996).…”

Section: Introductionmentioning

confidence: 54%

“…Figure 1 shows that the frequency of recombin-mutations in different transcription factors suppress either the hyper-recombination (Piruat and ation of hpr1Δ cells was 56.5 times above the wild-type value for the LY construct. However, hpr1Δ does not Santos-Rosa et al, 1996) or the ts phenotypes Uemura et al, 1996) of hpr1Δ and that hpr1Δhave a significant effect on the levels of recombination (deletions) of the L and LU direct repeat constructs. These dependent deletions between GAL10 repeats are stimulated under conditions of activation of transcription (Fan results indicate that the hyper-recombination phenotype produced by hpr1Δ is not general, but particular to DNA et al, 1996).…”

Section: Resultsmentioning

confidence: 93%

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Recombination between DNA repeats in yeast hpr1Delta cells is linked to transcription elongation

1997

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The induction of recombination by transcription activation has been documented in prokaryotes and eukaryotes. Unwinding of the DNA duplex, disruption of chromatin structure or changes in local supercoiling associated with transcription can be indirectly responsible for the stimulation of recombination. Here we provide genetic and molecular evidence for a specific mechanism of stimulation of recombination by transcription. We show that the induction of deletions between repeats in hpr1Δ cells of Saccharomyces cerevisiae is linked to transcription elongation. Molecular analysis of different direct repeat constructs reveals that deletions induced by hpr1Δ are specific for repeat constructs in which transcription initiating at an external promoter traverses particular regions of the DNA flanked by the repeats. Transcription becomes HPR1 dependent when elongating through such regions. Both the induction of deletions and the HPR1 dependence of transcription were abolished when a strong terminator was used to prevent transcription from proceeding through the DNA region flanked by the repeats. In contrast to previously reported cases of transcription‐induced recombination, there was no correlation between high levels of transcripts and high levels of recombination. Our study provides evidence that direct repeat recombination can be induced by transcriptional elongation.

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Section: Introductionmentioning

confidence: 54%

Section: Resultsmentioning

confidence: 93%

Recombination between DNA repeats in yeast hpr1Delta cells is linked to transcription elongation

1997

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“…ies were done essentially as described (Santos-Rosa et al, 1996) and will be described fully elsewhere (B.Clever, J.Schmuckli-Maurer and…”

Section: Methodsmentioning

confidence: 99%

“…Additional co‐immunoprecipitation experiments using cells not overexpressing Rad54p were done exactly as above but using 4 mg of whole cell extract. Purification of the recombinant His(6)‐Rad54 protein from E.coli cells transformed with pWDH251, production of polyclonal antisera in rabbits and immunoaffinity purification of antibodies were done essentially as described (Santos‐Rosa et al ., 1996) and will be described fully elsewhere (B.Clever, J.Schmuckli‐Maurer and W.‐D.Heyer, in preparation).…”

Section: Methodsmentioning

confidence: 99%

Recombinational repair in yeast: functional interactions between Rad51 and Rad54 proteins

et al. 1997

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Rad51p is a eukaryotic homolog of RecA, the central homologous pairing and strand exchange protein in Escherichia coli. Rad54p belongs to the Swi2p/Snf2p family of DNA‐stimulated ATPases. Both proteins are also important members of the RAD52 group which controls recombinational DNA damage repair of double‐strand breaks and other DNA lesions in Saccharomyces cerevisiae. Here we demonstrate by genetic, molecular and biochemical criteria that Rad51 and Rad54 proteins interact. Strikingly, overexpression of Rad54p can functionally suppress the UV and methyl methanesulfonate sensitivity caused by a deletion of the RAD51 gene. However, no suppression was observed for the defects of rad51 cells in the repair of γ‐ray‐induced DNA damage, mating type switching or spontaneous hetero‐allelic recombination. This suppression is genetically dependent on the presence of two other members of the recombinational repair group, RAD55 and RAD57. Our data provide compelling evidence that Rad51 and Rad54 proteins interact in vivo and that this interaction is functionally important for recombinational DNA damage repair. As both proteins are conserved throughout evolution from yeasts to humans, a similar protein–protein interaction may be expected in other organisms.

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“…Although the precise function of HPR1 and THO2 is not yet clear, their null mutations have consequences at transcription, suggesting that their functions may be related to RNAPII. This relationship is supported further by the identi®cation of suppressors of the hyper-recombination or thermosensitive phenotypes of hpr1D as mutations in genes related to RNAPII holoenzyme, such as HRS1/PGD1 and SRB2 (Piruat and Aguilera, 1996;Santos-Rosa et al, 1996) or SOH1, RPB2 and SUA7 (Fan et al, 1996), respectively. Importantly, Hpr1 has been found in association with Cdc73, Paf1 and Ccr4 in an alternative form of the RNAPII holoenzyme (Chang et al, 1999).…”

Section: Introductionmentioning

confidence: 96%

A protein complex containing Tho2, Hpr1, Mft1 and a novel protein, Thp2, connects transcription elongation with mitotic recombination in Saccharomyces cerevisiae

Chávez

2000

The EMBO Journal

281

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contributed equally to this work Transcription-induced recombination has been reported in all organisms from bacteria to mammals. We have shown previously that the yeast genes HPR1 and THO2 may be keys to the understanding of transcription-associated recombination, as they both affect transcription elongation and hyper-recombination in a concerted manner. Using a yeast strain that has the wild-type THO2 gene replaced by one encoding a His 6 -HA-tagged version, we have isolated an oligomeric complex containing four proteins: Tho2, Hpr1, Mft1 and a novel protein that we have named Thp2. We have reciprocally identi®ed a complex containing Hpr1, Tho2 and Mft1 using anti-Mft1 antibodies in immunoprecipitation experiments. The protein complex is mainly nuclear; therefore, Tho2 and Hpr1 are physically associated. Like hpr1D and tho2D cells, mft1D and thp2D cells show mitotic hyperrecombination and impaired transcription elongation, in particular, through the bacterial lacZ sequence. Hyper-recombination conferred by mft1D and thp2D is only observed in DNA regions under transcription conditions. We propose that this protein complex acts as a functional unit connecting transcription elongation with the incidence of mitotic recombination. Keywords: HPR1/THO2/MFT1/THP2/mitotic recombination/THO protein complex/transcriptionassociated recombination/transcription elongation Introduction Transcription of DNA may have different consequences for other DNA transactions such as DNA replication, repair and recombination. The relationship between transcription and recombination is of particular interest, given the importance of recombination in genomic instability and its link with cancer. Different reports from bacteria to mammals have shown that transcription induces recombination. Since Ikeda and Matsumoto (1979) ®rst showed that recombination of phage l in Escherichia coli was stimulated by Rpo-mediated transcription, other cases have been reported in prokaryotes (Dul and Drexler, 1988;Vilette et al., 1992). In yeast, the ®nding that HOT1, a cisacting hotspot of recombination, was dependent on RNA polymerase I (RNAPI)-driven transcription (VoelkelMeiman et al., 1987;Stewart and Roeder, 1989) provided the ®rst example of transcription-induced recombination. Subsequently, similar observations were made for RNA polymerase II (RNAPII)-driven transcription (Thomas and Rothstein, 1989;Grimm et al., 1991;Nevo-Caspi and Kupiec, 1994). In mammalian cells, RNAPII-driven transcription has been shown to stimulate homologous recombination (Nickoloff, 1992;Thyagarajan et al., 1995) and to positively control V(D)J recombination (Blackwell et al., 1986;Lauster et al., 1993;Oltz et al., 1993) and class switching (Daniels and Lieber, 1995).The identi®cation and analyses of the HPR1 and THO2 yeast genes have provided clues to understand transcription-associated recombination. HPR1 was identi®ed by a mutation conferring hyper-recombination between DNA repeats (Aguilera and Klein, 1988) and THO2 as a highcopy suppressor of hpr1D (Piruat and Aguilera...

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The Yeast HRS1 Gene Encodes a Polyglutamine-Rich Nuclear Protein Required for Spontaneous and hpr1-Induced Deletions Between Direct Repeats

Cited by 28 publications

References 0 publications

Recombination between DNA repeats in yeast hpr1Delta cells is linked to transcription elongation

Recombination between DNA repeats in yeast hpr1Delta cells is linked to transcription elongation

Recombinational repair in yeast: functional interactions between Rad51 and Rad54 proteins

A protein complex containing Tho2, Hpr1, Mft1 and a novel protein, Thp2, connects transcription elongation with mitotic recombination in Saccharomyces cerevisiae

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