DNA Repair Enzymes in Mammalian Cells

Abstract The damage profile produced by the reaction of singlet molecular oxygen with cellular DNA was determined using the comet assay associated with DNA repair enzymes. Singlet oxygen was produced intracellularly by thermal decomposition of a watersoluble endoperoxide of a naphthalene derivative which is able to penetrate through the membrane into mammalian cells. We found that the DNA modifications produced by singlet oxygen were almost exclusively oxidised purines recognised by the formamidopyrimidine DNA N-glycosylase. In contrast, significant amounts of direct strand breaks and alkalilabile sites or oxidised pyrimidines, detectable by the bacterial endonuclease III, were not produced.

Download Full-text

DASH-type cryptochromes – solved and open questions

Biological Chemistry ◽

10.1515/hsz-2020-0182 ◽

2020 ◽

Vol 401 (12) ◽

pp. 1487-1493

Author(s):

Stephan Kiontke ◽

Tanja Göbel ◽

Annika Brych ◽

Alfred Batschauer

Keyword(s):

Dna Repair ◽

Circadian Clock ◽

Blue Light ◽

Dna Repair Enzymes ◽

Repair Enzymes ◽

Open Questions ◽

Essential Components ◽

Repair Activity ◽

Almost All ◽

Uv Lesions

AbstractDrosophila, Arabidopsis, Synechocystis, human (DASH)-type cryptochromes (cry-DASHs) form one subclade of the cryptochrome/photolyase family (CPF). CPF members are flavoproteins that act as DNA-repair enzymes (DNA-photolyases), or as ultraviolet(UV)-A/blue light photoreceptors (cryptochromes). In mammals, cryptochromes are essential components of the circadian clock feed-back loop. Cry-DASHs are present in almost all major taxa and were initially considered as photoreceptors. Later studies demonstrated DNA-repair activity that was, however, restricted to UV-lesions in single-stranded DNA. Very recent studies, particularly on microbial organisms, substantiated photoreceptor functions of cry-DASHs suggesting that they could be transitions between photolyases and cryptochromes.

Download Full-text

p21Cip1/WAF1/Sdi1Does Not Affect Expression of Base Excision DNA Repair Enzymes During Chronic Oxidative Stress

Antioxidants and Redox Signaling ◽

10.1089/ars.2005.7.719 ◽

2005 ◽

Vol 7 (5-6) ◽

pp. 719-725 ◽

Cited By ~ 2

Author(s):

Michael A. O'Reilly ◽

Peter F. Vitiello ◽

Sean C. Gehen ◽

Rhonda J. Staversky

Keyword(s):

Oxidative Stress ◽

Dna Repair ◽

Dna Repair Enzymes ◽

Repair Enzymes ◽

Chronic Oxidative Stress ◽

Affect Expression ◽

Base Excision ◽

Base Excision Dna Repair

Download Full-text

Genotype Profiles of Loci Encoding DNA Repair Enzymes in Newborn and Elderly Populations: No Evidence of Association with Longevity

Biogerontology ◽

10.1007/s10522-005-6042-1 ◽

2006 ◽

Vol 7 (1) ◽

pp. 35-41 ◽

Cited By ~ 5

Author(s):

C. S. Wilding ◽

G. S. Rees ◽

C. L. Relton ◽

E. J. Tawn

Keyword(s):

Dna Repair ◽

Dna Repair Enzymes ◽

Repair Enzymes ◽

Elderly Populations

Download Full-text

Processivity of DNA repair enzymes

10.18699/sbpcd-2018-09 ◽

2018 ◽

pp. 16-16

Keyword(s):

Dna Repair ◽

Dna Repair Enzymes ◽

Repair Enzymes

Download Full-text

DNA damage shifts circadian clock time via Hausp-dependent Cry1 stabilization

eLife ◽

10.7554/elife.04883 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 45

Author(s):

Stephanie J Papp ◽

Anne-Laure Huber ◽

Sabine D Jordan ◽

Anna Kriebs ◽

Madelena Nguyen ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Circadian Clock ◽

Transcriptional Response ◽

Genotoxic Stress ◽

Genomic Integrity ◽

Clock Time ◽

Dna Repair Enzymes ◽

Repair Enzymes ◽

Specific Protease

The circadian transcriptional repressors cryptochrome 1 (Cry1) and 2 (Cry2) evolved from photolyases, bacterial light-activated DNA repair enzymes. In this study, we report that while they have lost DNA repair activity, Cry1/2 adapted to protect genomic integrity by responding to DNA damage through posttranslational modification and coordinating the downstream transcriptional response. We demonstrate that genotoxic stress stimulates Cry1 phosphorylation and its deubiquitination by Herpes virus associated ubiquitin-specific protease (Hausp, a.k.a Usp7), stabilizing Cry1 and shifting circadian clock time. DNA damage also increases Cry2 interaction with Fbxl3, destabilizing Cry2. Thus, genotoxic stress increases the Cry1/Cry2 ratio, suggesting distinct functions for Cry1 and Cry2 following DNA damage. Indeed, the transcriptional response to genotoxic stress is enhanced in Cry1−/− and blunted in Cry2−/− cells. Furthermore, Cry2−/− cells accumulate damaged DNA. These results suggest that Cry1 and Cry2, which evolved from DNA repair enzymes, protect genomic integrity via coordinated transcriptional regulation.

Download Full-text