Regulation of SOS mutagenesis by proteolysis.

Frank, Ekaterina G.; Ennis, Don G.; Gonzalez, Martín; Levine, Arthur S.; Woodgate, Roger

doi:10.1073/pnas.93.19.10291

Cited by 160 publications

(183 citation statements)

References 45 publications

Supporting

Mentioning

180

Contrasting

Order By: Relevance

“…RecA:ssDNA interacts with UmuD 2 to promote cleavage to UmuDЈ 2 (3), whereas UmuDЈ 2 C requires trans RecA:ssDNA for efficient TLS (9). UmuD 2 may be degraded by either Lon (10) or ClpXP proteases (11), whereas UmuDЈ 2 must first exchange into the UmuDЈD heterodimer to be degraded by ClpXP (12). The fact that such small proteins (no more than 30 kDa as dimers) can make so many specific protein-protein interactions is intriguing, and high-resolution structural studies were undertaken in an effort to find an explanation.…”

mentioning

confidence: 99%

Regulation of Escherichia coli SOS mutagenesis by dimeric intrinsically disordered umuD gene products

Simon

Sousa²,

Mohana‐Borges³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Products of the umuD gene in Escherichia coli play key roles in coordinating the switch from accurate DNA repair to mutagenic translesion DNA synthesis (TLS) during the SOS response to DNA damage. Homodimeric UmuD 2 is up-regulated 10-fold immediately after damage, after which slow autocleavage removes the Nterminal 24 amino acids of each UmuD. The remaining fragment, UmuD 2, is required for mutagenic TLS. The small proteins UmuD2 and UmuD 2 make a large number of specific protein-protein contacts, including three of the five known E. coli DNA polymerases, parts of the replication machinery, and RecA recombinase. We show that, despite forming stable homodimers, UmuD 2 and UmuD 2 have circular dichroism (CD) spectra with almost no ␣-helix or ␤-sheet signal at physiological concentrations in vitro. High protein concentrations, osmolytic crowding agents, and specific interactions with a partner protein can produce CD spectra that resemble the expected ␤-sheet signature. A lack of secondary structure in vitro is characteristic of intrinsically disordered proteins (IDPs), many of which act as regulators. A stable homodimer that lacks significant secondary structure is unusual but not unprecedented. Furthermore, previous single-cysteine cross-linking studies of UmuD 2 and UmuD 2 show that they have a nonrandom structure at physiologically relevant concentrations in vitro. Our results offer insights into structural characteristics of relatively poorly understood IDPs and provide a model for how the umuD gene products can regulate diverse aspects of the bacterial SOS response.natively unfolded ͉ SOS response ͉ unstructured ͉ denatured ͉ DNA repair

show abstract

mentioning

confidence: 99%

Regulation of Escherichia coli SOS mutagenesis by dimeric intrinsically disordered umuD gene products

Simon

Sousa²,

Mohana‐Borges³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Studies showed that RecA cleaved UmuD protein to a mutagenically active form (UmuD′) and that the UmuCD′ proteins form a complex with RecA and DNApol III. 6 This complex, referred to as a "mutasome," is thought to continue DNA synthesis past cyclo but edimers or bulky adducts. This "bypass" replication is error prone, allowing misinsertion of bases opposite the lesion, but it is thought to enhance survival by producing intact nascent strands.…”

Section: 3mentioning

confidence: 99%

“…Error-prone replication is thus referred to as a lesion-tolerance mechanism, employed in emergency conditions. 2,6 The mechanism used by the mutasome to induce DNApol III to by-pass lesions remains the subject of intense biochemical study. An often overlooked consequence of SOS mutagenesis is that at times of extreme duress there would be a rapid accumulation of mutations and enhanced genetic variation among the survivors.…”

Section: 3mentioning

confidence: 99%

“…These bulky adducts act as potent inducers of the SOS IJOCR response. 2,6 The induction of SOS can lead to the errorprone replication past a range of premutational lesions.…”

Section: Induced Mutagenesismentioning

confidence: 99%

“…In bacteria, it is called the save our soul (SOS) response involving the increased expression of a number of genes whose products not only assist the cell to survive DNA damage but also increase mutation rates. 2,6 Chemical mutagens are categorized into four general groups, based on the mechanism by which they interact with DNA. 3 1.…”

Section: Induced Mutagenesismentioning

confidence: 99%

See 2 more Smart Citations

Mutagenesis

Gupta¹,

Malu²,

Beera³

2017

IJOCRWEB

View full text Add to dashboard Cite

The “tale” of UmuD and its role in SOS mutagenesis†

Gonzalez

Woodgate

2002

BioEssays

View full text Add to dashboard Cite

Recently, the Escherichia coli umuD and umuC genes have been shown to encode E. coli's fifth DNA polymerase, pol V (consisting of a heterotrimer of UmuD'(2)C). The main function of pol V appears to be the bypass of DNA lesions that would otherwise block replication by pols I-IV. This process is error-prone and leads to a striking increase in mutations at sites of DNA damage. While the enzymatic properties of pol V are now only beginning to be fully appreciated, a great deal is known about how E. coli regulates the intracellular levels of the Umu proteins so that the lesion-bypassing activity of pol V is available to help cells survive the deleterious consequences of DNA damage, yet keeps any unwarranted activity on undamaged templates to a minimum. Our review summarizes the multiple restrictions imposed upon pol V, so as to limit its activity in vivo and, in particular, highlights the pivotal role that the N-terminal tail of UmuD plays in regulating SOS mutagenesis.

show abstract

Regulation of SOS mutagenesis by proteolysis.

Abstract: DNA damage-inducible mutagenesis in Escherichia coli is largely dependent upon the activity of the

Cited by 160 publications

References 45 publications

Regulation of Escherichia coli SOS mutagenesis by dimeric intrinsically disordered umuD gene products

Regulation of Escherichia coli SOS mutagenesis by dimeric intrinsically disordered umuD gene products

Mutagenesis

The “tale” of UmuD and its role in SOS mutagenesis†

Contact Info

Product

Resources

About