Molecular Mechanisms of the Whole DNA Repair System: A Comparison of Bacterial and Eukaryotic Systems

Morita, R; Nakane, Shuhei; Shimada, Atsuhiro; Inoue, Masao; Iino, Hitoshi; Wakamatsu, Taisuke; Fukui, Kenji; Nakagawa, Noriko; Masui, Ryoji; Kuramitsu, Seiki

doi:10.4061/2010/179594

Cited by 81 publications

(76 citation statements)

References 292 publications

(306 reference statements)

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“…Early reactions of MMR are performed by MutS and MutL proteins, which are widely conserved in species from bacteria to human (3,4). It is known that in human, mutations and epigenetic silencing of genes encoding MutS and MutL homologues cause Lynch syndrome, which is characterized by early-onset colorectal and other cancers (5)(6)(7)(8).…”

Section: Dna Mismatch Repair (Mmr)mentioning

confidence: 99%

Structural Features and Functional Dependency on β-Clamp Define Distinct Subfamilies of Bacterial Mismatch Repair Endonuclease MutL

Fukui

Baba

Kumasaka

et al. 2016

Journal of Biological Chemistry

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In early reactions of DNA mismatch repair, MutS recognizes mismatched bases and activates MutL endonuclease to incise the error-containing strand of the duplex. DNA sliding clamp is responsible for directing the MutL-dependent nicking to the newly synthesized/error-containing strand. In Bacillus subtilis MutL, the ␤-clamp-interacting motif (␤ motif) of the C-terminal domain (CTD) is essential for both in vitro direct interaction with ␤-clamp and in vivo repair activity. A large cluster of negatively charged residues on the B. subtilis MutL CTD prevents nonspecific DNA binding until ␤ clamp interaction neutralizes the negative charge. We found that there are some bacterial phyla whose MutL endonucleases lack the ␤ motif. For example, the region corresponding to the ␤ motif is completely missing in Aquifex aeolicus MutL, and critical amino acid residues in the ␤ motif are not conserved in Thermus thermophilus MutL. We then revealed the 1.35 Å-resolution crystal structure of A. aeolicus MutL CTD, which lacks the ␤ motif but retains the metalbinding site for the endonuclease activity. Importantly, there was no negatively charged cluster on its surface. It was confirmed that CTDs of ␤ motif-lacking MutLs, A. aeolicus MutL and T. thermophilus MutL, efficiently incise DNA even in the absence of ␤-clamp and that ␤-clamp shows no detectable enhancing effect on their activity. In contrast, CTD of Streptococcus mutans, a ␤ motif-containing MutL, required ␤-clamp for the digestion of DNA. We propose that MutL endonucleases are divided into three subfamilies on the basis of their structural features and dependence on ␤-clamp.

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Section: Dna Mismatch Repair (Mmr)mentioning

confidence: 99%

Structural Features and Functional Dependency on β-Clamp Define Distinct Subfamilies of Bacterial Mismatch Repair Endonuclease MutL

Fukui

Baba

Kumasaka

et al. 2016

Journal of Biological Chemistry

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“…Ökaryotik hücreler doğru zamanda doğru yerde, doğru faktörleri aktive etmek için geliştirilmiş stratejilere sahiptirler 4 . İnsanda DNA onarımında 130'dan fazla genin görev aldığı tahmin edilmektedir, bu sayı muhtemelen daha yüksektir, fakat bu genlerden sadece %50'sinin fonksiyonu bilinmektedir 6,9 .…”

Section: Dna Hasarıunclassified

“…Alkilasyonun, deaminasyonun, oksidasyonun ve DNA replikasyon hatalarının neden olduğu küçük DNA modifikasyonları önemli DNA tamir süreçlerinden birisi olan BER ile tamir edilmektedir 5,9,18 . BER mekanizması DNA glikozilaz, AP endonukleaz ya da AP DNA liyaz, DNA polimeraz ve DNA ligazı içeren enzimlerin fonksiyonunu gerektirmektedir 19 .…”

Section: 11baz Kesip-çıkarma Onarımı (Base Excision Repair) (Ber)unclassified

DNA Repair Mechanisms

Kurtoğlu¹,

Tekedereli²

2015

BSBD

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ÖZETİnsan genomik DNA'sının bütünlüğü, endojen ve ekzojen faktörlerin etkisiyle sürekli olarak tehdit altındadır. Bir memeli genomunda her gün yaklaşık olarak 104'ten daha fazla DNA hasarının ortaya çıktığı tahmin edilmektedir. Hasarın yoğunluğuna ve tipine bağlı olarak; hücre döngüsünün durdurulması, gen ifadesinin değişmesi, DNA tamirinin uyarılması, programlı hücre ölümü, kanser ya da yaşlanma gibi olaylar meydana gelebilmektedir. Hücreler genomik bütünlüğü korumak amacıyla karmaşık bir dizi DNA onarım mekanizmalarına sahiplerdir. Bu derlemede, DNA onarım mekanizmaları tartışılmıştır.Anahtar Kelimeler: DNA hasarı, Mutasyon, DNA onarım mekanizmaları SUMMARYThe integrity of human genomic DNA are constantly threatened by the action of endogenous and exogenous factors. It is estimated that more than 104 DNA lesions are occur in each mammalian cell each day. Depending on the intensity and type of the damage; cell cycle arrest, change in gene expression, stimulation of DNA repair, programmed cell death, cancer or cellular aging events may occur. To protect genomic integrity, cells have a complex network of DNA repair mechanisms. In this review, DNA repair mechanisms are discussed in general.

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“…Chk2 has also been shown to regulate apoptosis in a p53-dependent manner in vitro and in vivo in response to DNA damage (Seviour & Lin, 2010). Notably, the major recombinase of HR, Rad51, seems also to interact with p53, possibly serving as a tool for monitoring the extension as well the effectiveness of DNA repair processes (Henning & Sturzbecher Toxicology, 2003;Morita et al, 2010). Consequently, impaired DDR appears to have dramatic effects on both tumorigenesis and premature ageing.…”

Section: Apoptosis and Dna Damagementioning

confidence: 99%

Structure-Function Relationship of DNA Repair Proteins: Lessons from BRCA1 and RAD51 Studies

Boutou¹,

Pappa²,

Stuerzbecher³

et al. 2011

DNA Repair

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Molecular Mechanisms of the Whole DNA Repair System: A Comparison of Bacterial and Eukaryotic Systems

Cited by 81 publications

References 292 publications

Structural Features and Functional Dependency on β-Clamp Define Distinct Subfamilies of Bacterial Mismatch Repair Endonuclease MutL

Structural Features and Functional Dependency on β-Clamp Define Distinct Subfamilies of Bacterial Mismatch Repair Endonuclease MutL

DNA Repair Mechanisms

Structure-Function Relationship of DNA Repair Proteins: Lessons from BRCA1 and RAD51 Studies

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