From Wikipedia, the free encyclopedia
This article needs additional citations for . Please help
by . Unsourced material may be challenged and removed. (June 2011) ()
Gigabit Ethernet crossover cable ends
An Ethernet crossover cable is a
used to connect computing devices together directly. It is most often used to connect two devices of the same type: e.g. two computers (via their ) or two switches to each other. By contrast,
or straight through cables are used to connect devices of different types, such as a computer to a
Intentionally crossed wiring in the crossover cable connects the transmit signals at one end to the receive signals at the other end. Many devices today support
capability, wherein a patch cable can be used in place of a crossover cable, or vice versa, and the receive and transmit signals are reconfigured automatically within the devices to yield this desired result.
modular crossover adapter
Different type of crossover cable are required depending on the number of conductors in use by the Ethernet variant in use on the connection.
Ethernet standards use one wire pair for transmission in each direction. This requires that the transmit pair of each device be connected to the receive pair of the device on the other end. The 10BASE-T standard was devised to be used with existing
cable installations with straight-through connections, and so it required a simple scheme for plugging devices together.
device is connected to a switch or hub, this crossover is done internally in the switch or hub. A standard straight through cable is used for this purpose where each pin of the connector on one end is connected to the corresponding pin on the other connector.
One terminal may be connected directly to another without the use of a switch or hub, but in that case the crossover must be done in the cabling. Since 10BASE-T and 100BASE-TX use pairs 2 and 3, these two pairs must be swapped in the cable. This wiring scheme constitutes a crossover cable. A crossover cable may also be used to connect two hubs or two switches on their
Because the only difference between the
pin and pair assignments are that pairs 2 and 3 are swapped, a crossover cable may be envisioned as a cable with one
following T568A and the other T568B (see ). Such a cable will work for 10BASE-T or 100BASE-TX.
The polarity of each pair is not swapped, but the pairs crossed as a unit: the two wires within each pair are not crossed.
In a departure from both 10BASE-T and 100BASE-TX,
and faster use all four cable pairs for simultaneous transmission in both directions through the use of -like signal handling. For this reason, there are no dedicated transmit and receive pairs, and consequently, crossover cables are never required for 1000BASE-T, , , , and
communication. From 1000BASE-T onwards the physical medium attachment sublayer (PMA) provides identification of each pair and usually continues to work even over cable where the pairs are unusually swapped or crossed.
However, when connecting an 100BASE-TX or 10BASE-T device to a faster port, a crossover may still be required in very rare situations. Since there are both transmitters and receivers present on a 1000BASE-T and faster port on all pairs anyway, the
requires extremely little logic and is usually present.[]
Crossover cable connecting two MDI ports
In practice, it does not matter if non-crossover Ethernet cables are wired as T568A or T568B, just so long as both ends follow the same wiring format. Typical commercially available "pre-wired" cables can follow either format depending on the manufacturer. What this means is that one manufacturer's cables are wired one way and another's the other way, yet both are correct and will work. In either case, T568A or T568B, a normal (un-crossed) cable will have both ends wired identically according to the layout in either the Connection 1 column or the Connection 2 column.
Certain equipment or installations, including those in which phone and/or power are mixed with data in the same cable, may require that the "non-data" pairs 1 and 4 (pins 4, 5, 7 and 8) remain un-crossed.
Two pairs crossed, two pairs uncrossed
10BASE-T or 100BASE-TX crossover
Connection 1: T568A
Connection 2: T568B
Pins on plug face
white/green stripe
white/orange stripe
green solid
orange solid
white/orange stripe
white/green stripe
blue solid
blue solid
white/blue stripe
white/blue stripe
orange solid
green solid
white/brown stripe
white/brown stripe
brown solid
brown solid
variants of Ethernet, fibers are used in pairs with one fiber for each direction. Obviously, the one transmitter needs to be connected to the other receiver and vice versa. For this, fiber patch cables with
connectors are normally configured as crossover as well as the . Thus, a simple connection with two patch cables at each end and a section of fixed cable in the middle has got three crossovers in total, resulting in a working connection. Patch cable crossovers can usually be reconfigured very easily by swapping the
within a duplex bracket if required.
Introduced in 1998, this made the distinction between uplink and normal ports and manual selector switches on older hubs and switches obsolete. If one or both of two connected devices has the automatic MDI/MDI-X configuration feature, there is no need for crossover cables.
Although Auto MDI-X was specified as an optional feature in the , in practice it is implemented widely on most interfaces.
Besides the eventually agreed upon Automatic MDI/MDI-X, this feature may also be referred to by various vendor-specific terms including: Auto uplink and trade, Universal Cable Recognition and Auto Sensing.
Charles E. Spurgeon (2000). . O'Reilly Media. p. 247.  .
IEEE 802.3-2012 40.8.2 Crossover Function
IEEE 802.3-2012 40.1.4 Signaling
Daniel Dove (February 1998).
(PDF). Presentation to IEEE 802.3ab working group 2011.
Clause "40.4.4 Automatic MDI/MDI-X Configuration" in : ( (PDF). . p. 192. Implementation of an automatic MDI/MDI-X configuration is optional for 1000BASE-T devices.)
technologies
: Hidden categories:From Wikipedia, the free encyclopedia
In , crosslinking of DNA occurs when various exogenous or endogenous agents react with two
of , forming a covalent linkage between them. This crosslink can occur within the same strand (intrastrand) or between opposite strands of double-stranded DNA (interstrand). These adducts interfere with cellular metabolism, such as
and , triggering . These crosslinks can, however, be
through excision or recombination pathways.
DNA crosslinking also has useful merit in chemotherapy and targeting cancerous cells for apoptosis, as well as in understanding how proteins interact with DNA.
Intrastrand and interstrand crosslinking of DNA.
Many characterized crosslinking agents have two independently reactive groups within the same molecule, each of which is able to bind with a nucleotide residue of DNA. These agents are separated based upon their source of origin and labeled either as exogenous or endogenous. Exogenous crosslinking agents are chemicals and compounds, both natural and synthetic, that stem from environmental exposures, such as pharmaceuticals and cigarette smoke or automotive exhaust. Endogenous crosslinking agents are compounds and metabolites that are introduced from cellular or biochemical pathways within a cell or organism.
are exogenous
which react with the N7 position of guanine. These compounds have a bis-(2-ethylchloro)amine core structure, with a variable R-group, with the two reactive functional groups serving to alkylate nucleobases and form a crosslink lesion. These agents most preferentially form a 1,3 5'-d(GNC) interstrand crosslink. The introduction of this agent slightly bends the DNA duplex to accommodate for the agent's presence within the helix. These agents are often introduced as a pharmaceutical and are used in
(cis-diamminedichloroplatinum(II)) and its derivatives mostly act on adjacent guanines at their N7 positions. The planar compound links to nucleobases through water displacement of one or both of its chloride groups, allowing cisplatin to form monoadducts to DNA or RNA, intrastrand DNA crosslinks, interstrand DNA crosslinks, and DNA-protein crosslinks. When cisplatin generates DNA crosslinks, it more frequenlty forms 1,2-intrastrand crosslinks (5'-GG), but also forms 1,3-intrastrand crosslinks (5-GNG) at lower percentages. When cisplatin forms interstrand crosslinks (5'-GC), there is a severe distortion to the DNA helix due to a shortened distance between guanines on opposite strands and a cytosine that is flipped out of the helix as a consequence of the GG interaction. Similar to nitrogen mustards, cisplatin is used frequently in chemotherapy treatment - especially for testicular and ovarian cancers.
Chloro ethyl nitroso urea (CENU), specifically
(BCNU), are crosslinking agents that are widely used in chemotherapy, particularly for brain tumors. These agents differ from other crosslinkers as they alkylate O6 of guanine to form an O6-ethanoguanine. This intermediate compound then leads to an interstrand crosslink between a GC basepair. These crosslinking agents only result in small distortions to the DNA helix due to the molecules' smaller size.
are natural compounds (furocoumarins) present in plants. These compounds
into DNA at 5'-AT sequence sites and form
adducts when activated in the presence of . These covalent adducts are formed by linking the 3, 4 () or 4', 5’ () edge of psoralen to the 5, 6 double bond of . Psoralens can form two types of monoadducts and one diadduct (an interstrand crosslink) with . These adducts result in local distortions to DNA at the site of intercalation. Psoralens are used in the medical treatment of skin diseases, such as
(MMC) is from a class of antibiotics that are used broadly in chemotherapy, often with gastrointestinal related cancers. Mitomycin C can only act as a crosslinker when a DNA nucleotide has had a reduction to its
ring. When two dG's have been rearranged and methylated in this manner, a 5'-GC interstrand crosslink can be formed with the exo amines of each nucleobase. Mitomycin also harbors the ability to form monoadducts and intrastrand crosslinks with DNA as well. The interstrand crosslinks of Mitomycin C are formed in the minor groove of DNA, inducing a moderate widening or stretching to the DNA helix in order to accommodate for the presence of the molecule within the two strands.
is formed as a byproduct in the stomach from dietary sources of nitrites and can lead to crosslink lesions in DNA through the conversion of amino groups in DNA to carbonyls. This type of lesion occurs most frequently between two guanosines, with 1 of 4 deaminated guanosines resulting in an interstrand crosslink. It induces formation of interstrand DNA crosslinks at the
of exocyclic N2 of guanine at 5'-CG sequences. This lesion mildly distorts the double helix.
Bifunctional
are reactive chemicals that are formed endogenously via
biosynthesis. They create etheno adducts formed by
which undergo rearrangements to form crosslinks on opposite strands of DNA.
is a prototypical example that can crosslink DNA via two exocylcic guanine amino groups. Other aldehydes, such as
and , can introduce interstrand crosslinks and often act as exogenous agents as they are found in many processed foods. Often found within pesticides, tobacco smoke, and automotive exhaust, α,β unsaturated aldehydes, such as acrolein and crotonaldehyde, are further exogenous agents that may induce DNA crosslinks. Unlike other crosslinking agents, aldehyde-induced crosslinking is a intrinsically reversible process. NMR structure of these types of agents as interstrand crosslinks show that a 5'-GC adduct results in minor distortion to DNA, however a 5'-CG adduct destabilizes the helix and induces a bend and twist in the DNA.
DNA crosslinking lesions can also be formed when under conditions of oxidative stress, in which free oxygen radicals generate reactive intermediates in DNA, and these lesions have been implicated in aging and cancer. Tandem DNA lesions are formed at a substantial frequency by ionizing radiation and metal-catalyzed H2O2 reactions. Under anoxic conditions, the predominant double-base lesion is a species in which the C8 of guanine is linked to the 5-methyl group of an adjacent 3'-thymine (G[8,5- Me]T), forming intrastrand lesions.
Crosslinking Agent
Alkylating Agent
Crosslink Structure
Preferential Target Sequence
Nitrogen Mustard
I 5'-GC                  
Carmustine (BNCU)
I GC basepair
Mitomycin C
Malondialdehyde
I 5'-GC, 5'-CG
Oxidative Stress (and Radiation)
Nitrous Acid
Crosslinked DNA is repaired in cells by a combination of enzymes and other factors from the
(NER) pathway, , and the
(BER) pathway.To repair interstrand crosslinks in eukaryotes, a 3’ flap endonuclease from the NER, , is recruited to the crosslinked DNA, where it assists in ‘unhooking’ the DNA by cleaving the 3’ strand at the crosslink site. The 5’ strand is then cleaved, either by
or another , forming a
(DSB), which can then be repaired by the
DNA crosslinks generally cause loss of overlapping sequence information from the two strands of DNA. Therefore, accurate repair of the damage depends on retrieving the lost information from an undamaged
in the same cell. Retrieval can occur by pairing with a
produced during a preceding round of replication. In a
retrieval may also occur by pairing with a non-sister , as occurs especially during . Once pairing has occurred, the crosslink can be removed and correct information introduced into the damaged chromosome by homologous recombination.
Cleavage of the bond between a deoxyribose sugar in DNA’s sugar-phosphate backbone and its associated nucleobase leaves an abasic site in double stranded DNA. These abasic sites are often generated as an intermediate and then restored in base excision repair. However, if these sites are allowed to persist, they can inhibit DNA replication and transcription. Abasic sites can react with amine groups on proteins to form DNA-protein crosslinks or with exocyclic amines of other nucleobases to form interstrand crosslinks. To prevent interstrand or DNA-protein crosslinks, enzymes from the BER pathway tightly bind the abasic site and sequester it from nearby reactive groups, as demonstrated in human alkyladenine DNA glycosylase (AAG) and E. coli 3-methyladenine DNA glycosylase II (AlkA).
Treatment of E. coli with -plus-UV light () produces interstrand crosslinks in the cells’ DNA. Cole et al. and Sinden and Cole presented evidence that an
repair process requiring the products of genes , and
can remove these crosslinks in E. coli. This process appears to be quite efficient. Even though one or two unrepaired crosslinks are sufficient to inactivate a cell, a wild-type bacterial cell can repair and therefore recover from 53 to 71 psoralen crosslinks.
yeast cells are also inactivated by one remaining crosslink, but wild type yeast cells can recover from 120 to 200 crosslinks.
DNA-protein crosslinking can be caused by a variety of chemical and physical agents, including transition metals, ionizing radiation, and endogenous aldehydes, in addition to . Similar to DNA crosslinking, DNA-protein crosslinks are lesions in cells that are frequently damaged by UV radiation. The UV’s effect can lead to reactive interactions and cause DNA and the proteins that are in contact with it to crosslink. These crosslinks are very bulky and complex lesions. They primarily occur in areas of the chromosomes that are undergoing DNA replication and interfere with cellular processes.
The advancement in structure-identification methods has progressed, and the addition in the ability to measure interactions between DNA and protein is a requirement to fully understand the biochemical processes. The structure of DNA-protein complexes can be mapped by , which is the photoinduced formation of a covalent bond between two macromolecules or between two different parts of one macromolecule. The methodology involves covalently linking a DNA-binding motif of the target sequence-specific DNA-binding protein with a photoactivatable crosslinking agent capable of reacting with DNA nucleotides when exposed to UV. This method provides information on the interaction between the DNA and protein in the crosslink.
DNA repair pathways can result in the formation of .
treatments have been engineered using DNA cross-linking agents to interact with nitrogenous bases of DNA to block DNA replication. These cross-linking agents have the ability to act as single-agent therapies by targeting and destroying specific nucleotides in cancerous cells. This result is stopping the cycle and gr because it inhibits specific DNA repair pathways, this approach has a potential advantage in having fewer side effects.
In humans, the leading cause of cancer deaths worldwide is lung cancer, including
(NSLC) which accounts for 85% of all lung cancer cases in the United States. Individuals with NSLC are often treated with therapeutic platinum compounds (e.g. cisplatin, carboplatin or oxaliplatin) (see ) that cause interstrand DNA crosslinks. Among individuals with NSLC, low expression of the breast cancer 1 gene () in the primary tumor has correlated with improved survival after platinum-containing chemotherapy. This correlation implies that low BRCA1 in the cancer, and the consequent low level of DNA repair, causes vulnerability of the cancer to treatment by the DNA crosslinking agents. High BRCA1 may protect cancer cells by acting in the
repair pathway that removes the damages in DNA introduced by the platinum drugs. The level of BRCA1 expression is potentially an important tool for tailoring chemotherapy in lung cancer management.
Clinical chemotherapeutics can induce enzymatic and non-enzymatic DNA-protein crosslinks. An example of this induction is with platinum derivatives, such as cisplatin and oxaliplatin. They create non-enzymatic DNA-protein crosslinks through non-specific crosslinking of chromatin-interacting proteins to DNA. Crosslinking is also possible in other therapeutic agents by either stabilizing covalent DNA–protein reaction intermediates or by creating a pseudosubstrate, which traps the enzyme on DNA. Camptothecin derivatives, such as irinotecan and topotecan, target and trap specific DNA
1 (TOP1) by intercalating within the enzyme–DNA interface. Because the toxicity of these drugs depends on TOP1 trapping, cellular sensitivity to these compounds depends directly on TOP1 expression levels. As a result, the function of these drugs is to serve as enzyme poisons rather than inhibitors. This can be applied to treat tumor cells by utilizing TOP 2 enzyme poisons.
Guainazzi, A Sch?rer, Orlando D. (). . Cellular and Molecular Life Sciences. 67 (21): . :.  .
Cancer, Cleveland Clinic. . chemocare.com.
Jamieson, E. R.; Lippard, S. J. (). . Chemical Reviews. 99 (9): . :.  .  .
Poklar N, Pilch DS, Lippard SJ, Redding EA, Dunham SU, Breslauer KJ (July 1996). . Proc. Natl. Acad. Sci. U.S.A. 93 (15): 7606–11. :.   .  .
Rudd GN, Hartley JA, Souhami RL (1995). "Persistence of cisplatin-induced DNA interstrand crosslinking in peripheral blood mononuclear cells from elderly and young individuals". Cancer Chemother. Pharmacol. 35 (4): 323–6. :.  .
Coste, F.; Malinge, J. M.; Serre, L.; Shepard, W.; Roth, M.; Leng, M.; Zelwer, C. (). . Nucleic Acids Research. 27 (8): . :.  .  .
. National Cancer Institute.
Cimino, G. D.; Gamper, H. B.; Isaacs, S. T.; Hearst, J. E. (1985). . Annual Review of Biochemistry. 54: . :.  .  .
Qi Wu, Laura A Christensen, Randy J Legerski & Karen M Vasquez, Mismatch repair participates in error-free processing of DNA interstrand crosslinks in human cells,EMBO Reports 6, 6, 551–557 (2005).
Kirchner, James J.; Sigurdsson, Snorri T.; Hopkins, Paul B. (). . Journal of the American Chemical Society. 114 (11): . :.  .
Stone, Michael P.; Cho, Young-J Huang, H Kim, Hye-Y Kozekov, Ivan D.; Kozekova, A Wang, H Minko, Irina G.; Lloyd, R. Stephen (). . Accounts of Chemical Research. 41 (7): 793–804. :.  .
Niedernhofer, Laura J.; Daniels, J. S Rouzer, Carol A.; Greene, Rachel E.; Marnett, Lawrence J. (). . Journal of Biological Chemistry. 278 (33): 3. :.  .  .
Dooley, Patricia A.; Zhang, M Korbel, Gregory A.; Nechev, Lubomir V.; Harris, Constance M.; Stone, Michael P.; Harris, Thomas M. (). . Journal of the American Chemical Society. 125 (1): 62–72. :.  .  .
LC C P R AK Basu (2008). . Biochemistry. 47 (6): . :.   .  .
Box, Harold C.; Budzinski, Edwin E.; Dawidzik, Jean D.; Wallace, John C.; Evans, Marianne S.; Gobey, Jason S. (1996). . Radiation Research. 145 (5): 641–643. :.
Klein Douwel, D Boonen, Rick A.C.M.; Long, David T.; Szypowska, Anna A.; R?schle, M Walter, Johannes C.; Knipscheer, Puck. . Molecular Cell. 54 (3): 460–471. :.
Harris Bernstein, Carol Bernstein and Richard E. Michod (2011). Meiosis as an Evolutionary Adaptation for DNA Repair. Chapter 19 pages 357-382 in “DNA Repair” (Inna Kruman editor). InTech Open Publisher. DOI: 10.  
. Friedberg, Errol C., Friedberg, Errol C. (2nd ed.). Washington, D.C.: ASM Press. 2006.  .  .
Admiraal, Suzanne J.; O’Brien, Patrick J. (). . Biochemistry. 54 (9): . :.  .
Cole RS, Levitan D, Sinden RR (1976). "Removal of psoralen interstrand cross-links from DNA of Escherichia coli: mechanism and genetic control". J. Mol. Biol. 103 (1): 39–59. :.  .
Sinden RR, Cole RS (1978). . J. Bacteriol. 136 (2): 538–47.   .  .
Noll DM, Mason TM, Miller PS (2006). . Chem. Rev. 106 (2): 277–301. :.   .  .
Tretyakova, N Groehler, A Ji, Shaofei. .
Pendergrast, P.; Chen, Y Ebright, Y Ebright, Richard.
Smith, K Martin, Shetlar. .
Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA (2008). . Mayo Clin. Proc. 83 (5): 584–94. :.   .  .
Taron M, Rosell R, Felip E, Mendez P, Souglakos J, Ronco MS, Queralt C, Majo J, Sanchez JM, Sanchez JJ, Maestre J (2004). "BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer". Hum. Mol. Genet. 13 (20): 2443–9. :.  .
Papadaki C, Sfakianaki M, Ioannidis G, Lagoudaki E, Trypaki M, Tryfonidis K, Mavroudis D, Stathopoulos E, Georgoulias V, Souglakos J (2012). "ERCC1 and BRAC1 mRNA expression levels in the primary tumor could predict the effectiveness of the second-line cisplatin-based chemotherapy in pretreated patients with metastatic non-small cell lung cancer". J Thorac Oncol. 7 (4): 663–71. :.  .
Stingele, J Bellelli, R Boulton, Simon. .
- Interactive structure for cisplatin and DNA adduct formation
- Interactive structure for psoralen and crosslinked DNA
Psoralen Ultraviolet A Light Treatment
This is a user sandbox of . A user sandbox is a subpage of the user's . It serves as a testing spot and page development space for the user and is not an encyclopedia article.
This template should only be used in the user namespace.
: Hidden categories:}