Grover Norquist Americans for Tax Reform How was Norquist involved with tax reform? Norquist is best known for founding Americans for Tax Reform (ATR) what did ATR do? The primary policy goal of Americans for Tax Reform is to reduce government revenues as a percentage of the GDP.
What else is significant about ATR?
Aside from being the primary goal  to reduce government revenues as a percentage of the GDP what else is significant about ATR?
Norquist is best known for founding Americans for Tax Reform (ATR) in 1985, which he says was done at the request of then-President Ronald Reagan. Referring to Norquist's activities as head of ATR, Steve Kroft, in a 60 Minutes episode that aired on November 20, 2011, claimed that "Norquist has been responsible, more than anyone else, for rewriting the dogma of the Republican Party."  The primary policy goal of Americans for Tax Reform is to reduce government revenues as a percentage of the GDP. ATR states that it "opposes all tax increases as a matter of principle." Americans for Tax Reform has supported Taxpayer Bill of Rights (TABOR) legislation and transparency initiatives, while opposing cap-and-trade legislation and efforts to regulate health care.  In 1993, Norquist launched his Wednesday Meeting series at ATR headquarters, initially to help fight President Clinton's healthcare plan. The meeting eventually became one of the most significant institutions in American conservative political organizing. The meetings have been called "a must-attend event for Republican operatives fortunate enough to get an invitation", and "the Grand Central station of the conservative movement." Medvetz (2006) argues that the meetings have been significant in "establishing relations of...exchange" among conservative subgroups and "sustaining a moral community of conservative activists."  As a nonprofit organization, Americans for Tax Reform is not required to disclose the identity of its contributors. Critics, such as Sen. Alan Simpson, have asked Norquist to disclose his contributors; he has declined but has said that ATR is financed by direct mail and other grassroots fundraising efforts. According to CBS News, "a significant portion appears to come from wealthy individuals, foundations and corporate interests." CANNOTANSWER
As a nonprofit organization, Americans for Tax Reform is not required to disclose the identity of its contributors.
Grover Glenn Norquist (born October 19, 1956) is an American political activist and tax reduction advocate who is founder and president of Americans for Tax Reform, an organization that opposes all tax increases. A Republican, he is the primary promoter of the Taxpayer Protection Pledge, a pledge signed by lawmakers who agree to oppose increases in marginal income tax rates for individuals and businesses, as well as net reductions or eliminations of deductions and credits without a matching reduced tax rate. Prior to the November 2012 election, the pledge was signed by 95% of all Republican members of Congress and all but one of the candidates running for the 2012 Republican presidential nomination.

Early life and education
Norquist grew up in Weston, Massachusetts. He is the son of Carol (née Lutz) and Warren Elliott Norquist (a vice president of Polaroid Corporation), and is of Swedish ancestry. His brother, David Norquist has served in senior posts in Republican administrations at both the United States Department of Defense and the United States Department of Homeland Security. Norquist became involved with politics at an early age when he volunteered for the 1968 Nixon campaign, assisting with get out the vote efforts. He graduated from Weston High School and enrolled at Harvard University in 1974, where he earned his A.B. and M.B.A.

At college, Norquist was an editor at the Harvard Crimson and helped to publish the libertarian-leaning Harvard Chronicle. He was a member of the Hasty Pudding Theatricals. Norquist has said: "When I became 21, I decided that nobody learned anything about politics after the age of 21." He attended the Leadership Institute in Arlington, Virginia, an organization that teaches conservative Americans how to influence public policy through activism and leadership.

Career

Early career

Early in his career, Norquist was executive director of both the National Taxpayers Union and the national College Republicans, holding both positions until 1983. He served as Economist and Chief Speechwriter at the U.S. Chamber of Commerce from 1983 to 1984.

Norquist traveled to several war zones to help support anti-Soviet guerrilla armies in the second half of the 1980s. He worked with a support network for Oliver North's efforts with the Nicaraguan Contras and other insurgencies, in addition to promoting U.S. support for groups including Mozambique's RENAMO and Jonas Savimbi's UNITA in Angola and helping to organize anti-Soviet forces in Laos. In 1985, he went to a conference in South Africa sponsored by South African businesses called the "Youth for Freedom Conference", which sought to bring American and South African conservatives together to end the anti-apartheid movement. Norquist represented the France-Albert Rene government of Seychelles as a lobbyist from 1995 until 1999. Norquist's efforts were the subject of Tucker Carlson's 1997 article in The New Republic, "What I sold at the revolution."

Americans for Tax Reform
Norquist is best known for founding Americans for Tax Reform (ATR) in 1985, which he says was done at the request of then-President Ronald Reagan. Referring to Norquist's activities as head of ATR, Steve Kroft, in a 60 Minutes episode that aired on November 20, 2011, claimed that "Norquist has been responsible, more than anyone else, for rewriting the dogma of the Republican Party."

The primary policy goal of Americans for Tax Reform is to reduce government revenues as a percentage of the GDP. ATR states that it "opposes all tax increases as a matter of principle." Americans for Tax Reform has supported Taxpayer Bill of Rights (TABOR) legislation and transparency initiatives, while opposing cap-and-trade legislation and efforts to regulate health care.

In 1993, Norquist launched his Wednesday Meeting series at ATR headquarters, initially to help fight President Clinton's healthcare plan. The meeting eventually became one of the most significant institutions in American conservative political organizing. The meetings have been called "a must-attend event for Republican operatives fortunate enough to get an invitation", and "the Grand Central station of the conservative movement." Medvetz (2006) argues that the meetings have been significant in "establishing relations of ... exchange" among conservative subgroups and "sustaining a moral community of conservative activists."

As a nonprofit organization, Americans for Tax Reform is not required to disclose the identity of its contributors. Critics, such as Sen. Alan Simpson, have asked Norquist to disclose his contributors; he has declined but has said that ATR is financed by direct mail and other grassroots fundraising efforts. According to CBS News, "a significant portion appears to come from wealthy individuals, foundations and corporate interests."

Taxpayer Protection Pledge
Prior to the November 2012 election, 238 of 242 House Republicans and 41 out of 47 Senate Republicans had signed ATR's "Taxpayer Protection Pledge", in which the pledger promises to "oppose any and all efforts to increase the marginal income tax rate for individuals and business; and to oppose any net reduction or elimination of deductions and credits, unless matched dollar for dollar by further reducing tax rates."

The November 6, 2012 elections resulted in a decline in the number of Taxpayer Protection Pledge signatories in both the upper and lower houses of the 113th Congress: from 41 to 39 in the Senate, and from 238 to "fewer than ... 218" in the House of Representatives. According to journalist Alex Seitz-Wald, losses in the election by Norquist supporters and the "fiscal cliff" have emboldened and made more vocal critics of Norquist.

In November 2011, Senate Majority leader Harry Reid (D-NV) blamed Norquist's influence for the Joint Select Committee on Deficit Reduction's lack of progress, claiming that Congressional Republicans "are being led like puppets by Grover Norquist. They're giving speeches that we should compromise on our deficit, but never do they compromise on Grover Norquist. He is their leader." Since Norquist's pledge binds signatories to opposing deficit reduction agreements that include any element of increased tax revenue, some Republican deficit hawks now retired from office have stated that Norquist has become an obstacle to deficit reduction. Former Republican Senator Alan Simpson (R-WY), co-chairman of the National Commission on Fiscal Responsibility and Reform, has been particularly critical, describing Norquist's position as "[n]o taxes, under any situation, even if your country goes to hell."

Other political activities

National politics

Norquist was listed as one of the five primary leaders of the post-Goldwater conservative movement by Nina Easton in her 2000 book, Gang of Five. Working with eventual Speaker Newt Gingrich, Norquist was one of the co-authors of the 1994 Contract with America, and helped to rally grassroots efforts, which Norquist later chronicled in his book Rock the House. Norquist also served as a campaign staff member on the 1988, 1992 and 1996 Republican Platform Committees.

Norquist was instrumental in securing early support for the presidential campaign of then-Texas Governor George W. Bush, acting as his unofficial liaison to the conservative movement. He campaigned for Bush in both 2000 and 2004. After Bush's first election, Norquist was a key figure involved in crafting Bush's tax cuts. John Fund of the Wall Street Journal dubbed Norquist "the Grand Central Station" of conservatism and told The Nation: "It's not disputable" that Norquist was the key to the Bush campaign's surprising level of support from movement conservatives in 2000.

He has long been active in building bridges between various ethnic and religious minorities and the free-market community through his involvement with Acton Institute, Christian Coalition and Toward Tradition.

He has also "announced his plan to assemble a center-right coalition to discuss pulling out of Afghanistan to save hundreds of billions of dollars."

Norquist is active in Tea Party politics. Talking at a Florida rally he said "tea party groups should serve as the 'exoskeleton' that protects newly elected Republicans" from pressures to increase government spending.

Comprehensive immigration reform is an interest of Norquist's, who believes that the United States should have "dramatically higher levels of immigration" than it currently does.

Involvement with Jack Abramoff
According to a 2011 memoir by former lobbyist Jack Abramoff, Norquist was one of Abramoff's first major Republican party contacts. Norquist and Americans for Tax Reform were also mentioned in Senate testimony relating to the Jack Abramoff Indian lobbying scandal which resulted in a 2006 guilty plea by Abramoff to three criminal felony counts of defrauding of American Indian tribes and corrupting public officials. Records released by the Senate Indian Affairs Committee allege that ATR served as a "conduit" for funds that flowed from Abramoff's clients to surreptitiously finance grass-roots lobbying campaigns. Norquist has denied that he did anything wrong, and has not been charged with any crime.

State and local politics

Norquist's national strategy has included recruiting state and local politicians to support ATR's stance on taxes. Norquist has helped to set up regular meetings for conservatives in many states. These meetings are modeled after his Wednesday meetings in Washington, with the goal of creating a nationwide network of conservative activists that he can call upon to support conservative causes, such as tax cuts and deregulation. There are now meetings in 48 states.

In 2004, Norquist helped California Governor Arnold Schwarzenegger with his plan to privatize the CalPERS system. In Virginia's 2005 Republican primaries, Norquist encouraged the defeat of a number of legislators who voted for higher taxes.

Boards and other activities
Norquist serves on the boards of directors of numerous organizations including the National Rifle Association, the American Conservative Union, the Hispanic Leadership Fund, the Indian-American Republican Caucus, and ParentalRights.org, an organization that wishes to add a Parental Rights Amendment to the United States Constitution. In 2010, Norquist joined the advisory board of GOProud, a political organization representing lesbian, gay, bisexual, and transgender conservatives and their allies, for which he was criticized by the Family Research Council. Norquist also sits on a six-person advisory panel that nominates [[Time Person of the Year|Time'''s Person of the Year]]. In business, Norquist was a co-founder of the Merritt Group, later renamed Janus-Merritt Strategies. He is a member of the Council on Foreign Relations. Norquist signed the Madrid Charter, a document drafted by the conservative Spanish political party Vox that describes left-wing groups as enemies of Ibero-America involved in a "criminal project" that are "under the umbrella of the Cuban regime".

Views on government
Norquist favors dramatically reducing the size of government. He has been noted for his widely quoted quip from a 2001 interview with NPR's Morning Edition:

Journalist William Greider quotes him saying his goal is to bring America back to what it was "up until Teddy Roosevelt, when the socialists took over. The income tax, the death tax, regulation, all that." When asked by journalist Steven Kroft about the goal of chopping government "in half and then shrink it again to where we were at the turn of the [20th] century" before Social Security and Medicare, Norquist replied, "We functioned in this country with government at eight percent of GDP for a long time and quite well."

Some smaller government advocates argue that Norquist's "obsession with tax revenue" is actually counterproductive with respect to minimizing the size of government. Although the Americans for Tax Reform mission statement is "The government's power to control one's life derives from its power to tax. We believe that power should be minimized", critics at the Cato Institute have argued that "holding the line on taxes constrains only one of the four tools (taxes, tax deductions, spending without taxation, and regulation) used by government to alter economic outcomes."

Norquist published Leave Us Alone: Getting the Government's Hands Off Our Money, Our Guns, Our Lives, in 2008. In 2012, he published Debacle: Obama's War on Jobs and Growth and What We Can Do Now to Regain Our Future, with John R. Lott, Jr. He has served as a monthly "Politics" columnist and contributing editor to The American Spectator.

Norquist has also called for reductions in defense spending as one way to reduce the size of government.

Norquist has endorsed a non-interventionist foreign policy and cuts to the US military budget.

Personal life
Norquist has described himself as a "boring white bread Methodist." In 2004, at age 48, he married a Palestinian Muslim named Samah Alrayyes, a Kuwaiti PR specialist who was formerly a director of the Islamic Free Market Institute and specialist at the Bureau of Legislative and Public Affairs at United States Agency for International Development (USAID). The couple has adopted two children, both girls, one of whom is from the city of Bethlehem.

According to friend and former roommate John Fund, Norquist's devotion to his political causes is "monk-like" and comparable to that of Ralph Nader.

Norquist has competed three times in the comedy fundraiser "Washington's Funniest Celebrity" and placed second in 2009. Humorist P. J. O'Rourke has described Norquist as "Tom Paine crossed with Lee Atwater plus just a soupçon of Madame Defarge".

Norquist and his wife attended the annual Burning Man festival in August 2014 in Black Rock, Nevada. Norquist explained that he wished to attend because, "There's no government that organizes this. That's what happens when nobody tells you what to do. You just figure it out. So Burning Man is a refutation of the argument that the state has a place in nature."

Writings
 Rock the House. Ft. Lauderdale, Fla: VYTIS Press, 1995. 
 Taxes: The Economic & Philosophical Necessity of Real Reform. Minneapolis, MN: Center of the American Experiment, 1996. 
 "America is freedom" chapter from Deaver, Michael K. Why I Am a Reagan Conservative, Chapter New York: W. Morrow, 2005. 
 Leave Us Alone: Getting the Government's Hands Off Our Money, Our Guns, Our Lives. New York, NY: W. Morrow, 2008. 
 Debacle: Obama's War on Jobs and Growth and What We Can Do Now to Regain Our Future. Hoboken, NJ: John Wiley & Sons, Inc., 2012. 

See also
 Democratic International
 K Street Project
 Starve the beast

References

External links

 Official biography from Americans for Tax Reform
 Column archive at National Review Online Column archive at The Guardian 
 
 
 
 
 Transcript: "Bill Moyers Interviews Grover Norquist", NOW with Bill Moyers, January 10, 2003
 Grover Norquist on Leave Us Alone, National Review Online, 2008(?)
 "The Pledge: Grover Norquist's hold on the GOP", 60 Minutes'', November 20, 2011, video interview and related reports
 A Lesson in Conservative Optimism, The Weekend Interview by Stephen Moore, The Wall Street Journal, November 23, 2012

1956 births
20th-century American male writers
20th-century American non-fiction writers
20th-century Methodists
21st-century American male writers
21st-century American non-fiction writers
21st-century Methodists
Activists from Massachusetts
American columnists
American libertarians
American lobbyists
American male non-fiction writers
American Methodists
American people of Swedish descent
American political writers
The American Spectator people
Christian libertarians
College Republicans
Harvard Business School alumni
Harvard Advocate alumni
Harvard College alumni
The Harvard Crimson people
Hasty Pudding alumni
Living people
Massachusetts Republicans
Members of the Council on Foreign Relations 
Non-interventionism
Pennsylvania Republicans
People from Washington, D.C.
People from Weston, Massachusetts
Signers of the Madrid Charter
Tea Party movement activists
Washington, D.C. Republicans
Writers from Massachusetts
Writers from Washington, D.C.
Weston High School (Massachusetts) alumni
Serine/threonine-protein kinase ATR also known as ataxia telangiectasia and Rad3-related protein (ATR) or FRAP-related protein 1 (FRP1) is an enzyme that, in humans, is encoded by the ATR gene. It is a large kinase of about 301.66 kDa. ATR belongs to the phosphatidylinositol 3-kinase-related kinase protein family. ATR is activated in response to single strand breaks, and works with ATM to ensure genome integrity.

Function 

ATR is a serine/threonine-specific protein kinase that is involved in sensing DNA damage and activating the DNA damage checkpoint, leading to cell cycle arrest in eukaryotes. ATR is activated in response to persistent single-stranded DNA, which is a common intermediate formed during DNA damage detection and repair.  Single-stranded DNA occurs at stalled replication forks and as an intermediate in DNA repair pathways such as nucleotide excision repair and homologous recombination repair.  ATR is activated during more persistent issues with DNA damage; within cells, most DNA damage is repaired quickly and faithfully through other mechanisms. ATR works with a partner protein called ATRIP to recognize single-stranded DNA coated with RPA. RPA binds specifically to ATRIP, which the recruits ATR through an ATR activating domain (AAD) on its surface. This association of ATR with RPA is how ATR specifically binds to and works on single-stranded DNA—this was proven through experiments with cells that had mutated nucleotide excision pathways. In these cells, ATR was unable to activate after UV damage, showing the need for single stranded DNA for ATR activity. The acidic alpha-helix of ATRIP binds to a basic cleft in the large RPA subunit to create a site for effective ATR binding. Many other proteins exist that are recruited to the cite of ssDNA that are needed for ATR activation. While RPA recruits ATRIP, the RAD9-RAD1-HUS1 (9-1-1) complex is loaded onto the DNA adjacent to the ssDNA; though ATRIP and the 9-1-1 complex are recruited independently to the site of DNA damage, they interact extensively through massive phosphorylation once colocalized. The 9-1-1 complex, a ring-shaped molecule related to PCNA, allows the accumulation of ATR in a damage specific way. For effective association of the 9-1-1 complex with DNA, RAD17-RFC is also needed.   This complex also brings in topoisomerase binding protein 1 (TOPBP1) which binds ATR through a highly conserved AAD. TOPBP1 binding is dependent on the phosphorylation of the Ser387 residue of the RAD9 subunit of the 9-1-1 complex. This is likely one of the main functions of the 9-1-1 complex within this DNA damage response. Another important protein that binds TR was identified by Haahr et al. in 2016: Ewings tumor-associated antigen 1 (ETAA1). This protein works in parallel with TOPBP1 to activate ATR through a conserved AAD. It is hypothesized that this pathway, which works independently of TOPBP1 pathway, is used to divide labor and possibly respond to differential needs within the cell. It is hypothesized that one pathway may be most active when ATR is carrying out normal support for replicating cells, and the other may be active when the cell is under more extreme replicative stress.

It is not just ssDNA that activates ATR, though the existence of RPA associated ssDNA is important. Instead, ATR activation is heavily dependent on the existence of all the proteins previously described, that colocalize around the site of DNA damage. An experiment where RAD9, ATRIP, and TOPBP1 were overexpressed proved that these proteins alone were enough to activate ATR in the absence of ssDNA, showing their importance in triggering this pathway.

Once ATR is activated, it phosphorylates Chk1, initiating a signal transduction cascade that culminates in cell cycle arrest. It acts to activate Chk1 through a claspin intermediate which binds the two proteins together. This claspin intermediate needs to be phosphorylated at two sites in order to do this job, something that can be carried out by ATR but is most likely under the control of some other kinase. This response, mediated by Chk1, is essential to regulating replication within a cell; through the Chk1-CDC25 pathway, which effects levels of CDC2, this response is thought to reduce the rate of DNA synthesis in the cell and inhibit origin firing during replication. In addition to its role in activating the DNA damage checkpoint, ATR is thought to function in unperturbed DNA replication. The response is dependent on how much ssDNA accumulates at stalled replication forks. ATR is activated during every S phase, even in normally cycling cells, as it works to monitor replication forks to repair and stop cell cycling when needed.  This means that ATR is activated at normal, background levels within all healthy cells. There are many points in the genome that are susceptible to stalling during replication due to complex sequences of DNA or endogenous damage that occurs during the replication. In these cases, ATR works to stabilize the forks so that DNA replication can occur as it should.

ATR is related to a second checkpoint-activating kinase, ATM, which is activated by double strand breaks in DNA or chromatin disruption. ATR has also been shown to work on double strand breaks (DSB), acting a slower response to address the common end resections that occur in DSBs, and thus leave long strands of ssDNA (which then go on to signal ATR). In this circumstance, ATM recruits ATR and they work in partnership to respond to this DNA damage. They are responsible for the “slow” DNA damage response that can eventually trigger p53 in healthy cells and thus lead to cell cycle arrest or apoptosis.

ATR as an essential protein 
Mutations in ATR are very uncommon. The total knockout of ATR is responsible for early death of mouse embryos, showing that it is a protein with essential life functions. It is hypothesized that this could be related to its likely activity in stabilizing Okazaki fragments on the lagging strands of DNA during replication, or due to its job stabilizing stalled replication forks, which naturally occur. In this setting, ATR is essential to preventing fork collapse, which would lead to extensive double strand breakage across the genome. The accumulation of these double strand breaks could lead to cell death.

Clinical significance 

Mutations in ATR are responsible for Seckel syndrome, a rare human disorder that shares some characteristics with ataxia telangiectasia, which results from ATM mutation.

ATR is also linked to familial cutaneous telangiectasia and cancer syndrome.

Inhibitors 

ATR/ChK1 inhibitors can potentiate the effect of DNA cross-linking agents such as cisplatin and nucleoside analogues such as gemcitabine. The first clinical trials using inhibitors of ATR have been initiated by AstraZeneca, preferably in ATM-mutated chronic lymphocytic leukaemia (CLL), prolymphocytic leukaemia (PLL) or B-cell lymphoma patients and by Vertex Pharmaceuticals in advanced solid tumours. ATR provided and exciting point for potential targeting in these solid tumors, as many tumors function through activating the DNA damage response. These tumor cells rely on pathways like ATR to reduce replicative stress within the cancerous cells that are uncontrollably dividing, and thus these same cells could be very susceptible to ATR knockout. In ATR-Seckel mice, after exposure to cancer-causing agents, the damage DNA damage response pathway actually conferred resistance to tumor development (6). After many screen to identify specific ATR inhibitors, currently four made it into phase I or phase II clinical trials since 2013; these include AZD6738, M6620 (VX-970), BAY1895344, and M4344 (VX-803) (10). These ATR inhibitors work to help the cell proceed through p53 independent apoptosis, as well as force mitotic entry that leads to mitotic catastrophe.

One study by Flynn et al. found that ATR inhibitors work especially well in cancer cells which rely on the alternative lengthening of telomeres (ALT) pathway. This is due to RPA presence when ALT is being established, which recruits ATR to regulate homologous recombination. This ALT pathway was extremely fragile with ATR inhibition and thus using these inhibitors to target this pathway that keeps cancer cell immortal could provide high specificity to stubborn cancer cells.

Examples include

 Berzosertib

Aging
Deficiency of ATR expression in adult mice leads to the appearance of age-related alterations such as hair graying, hair loss, kyphosis (rounded upper back), osteoporosis and thymic involution.  Furthermore, there are dramatic reductions with age in tissue-specific stem and progenitor cells, and exhaustion of tissue renewal and homeostatic capacity.  There was also an early and permanent loss of spermatogenesis.  However, there was no significant increase in tumor risk.

Seckel syndrome
In humans, hypomorphic mutations (partial loss of gene function) in the ATR gene are linked to Seckel syndrome, an autosomal recessive condition characterized by proportionate dwarfism, developmental delay, marked microcephaly, dental malocclusion and thoracic kyphosis.  A senile or progeroid appearance has also been frequently noted in Seckel patients. For many years, the mutation found in the two families first diagnosed with Seckel Syndrome were the only mutations known to cause the disease.

In 2012, Ogi and colleagues discovered multiple new mutations that also caused the disease. One form of the disease, which involved mutation in genes encoding the ATRIP partner protein, is considered more severe that the form that was first discovered. This mutation led to sever microcephaly and growth delay, microtia, micrognathia, dental crowding, and skeletal issues (evidenced in unique patellar growth). Sequencing revealed that this ATRIP mutation occurred most likely due to missplicing which led to fragments of the gene without exon 2. The cells also had a nonsense mutation in exon 12 of the ATR gene which led to a truncated ATR protein. Both of these mutations resulted in lower levels of ATR and ATRIP than in wild-type cells, leading to insufficient DNA damage response and the severe form of Seckel Syndrome noted above.

Researchers also found that heterozygous mutations in ATR were responsible for causing Seckel Syndrome. Two novel mutations in one copy of the ATR gene caused under-expression of both ATR and ATRIP.

Homologous recombinational repair

Somatic cells of mice deficient in ATR have a decreased frequency of homologous recombination and an increased level of chromosomal damage.  This finding implies that ATR is required for homologous recombinational repair of endogenous DNA damage.

Drosophila mitosis and meiosis
Mei-41 is the Drosophila ortholog of ATR.  During mitosis in Drosophila DNA damages caused by exogenous agents are repaired by a homologous recombination process that depends on mei-41(ATR).  Mutants defective in mei-41(ATR) have increased sensitivity to killing by exposure to the DNA damaging agents UV , and methyl methanesulfonate.  Deficiency of mei-41(ATR) also causes reduced spontaneous allelic recombination (crossing over) during meiosis suggesting that wild-type mei-41(ATR) is employed in recombinational repair of spontaneous DNA damages during meiosis.

Interactions 

Ataxia telangiectasia and Rad3-related protein has been shown to interact with:

 BRCA1, 
 CHD4, 
 HDAC2, 
 MSH2, 
 P53 
 RAD17,  and
 RHEB.

References

Further reading

External links 
 Drosophila meiotic-41 - The Interactive Fly
 

Proteins
EC 2.7.11 Alpha-thalassemia mental retardation syndrome (ATRX), also called alpha-thalassemia X-linked intellectual disability syndrome, nondeletion type or ATR-X syndrome, is an X-linked recessive condition associated with a mutation in the ATRX gene. Males with this condition tend to be moderately intellectually disabled and have physical characteristics including coarse facial features, microcephaly (small head size), hypertelorism (widely spaced eyes), a depressed nasal bridge, a tented upper lip and an everted lower lip. Mild or moderate anemia, associated with alpha-thalassemia, is part of the condition. Females with this mutated gene have no specific signs or features, but if they do, they may demonstrate skewed X chromosome inactivation.

Atr-X Syndrome can also come with problems regulating Co2 Levels and normal bodily temperature regulation, the cause of this is widely debated but currently unknown, many children with Atr-X may need oxygen support long term through their entire life but cases that require long term oxygen are rare, however many children with Atr-x will require help with feeding such and NG/NJ tube feeding, this is not present in all cases however. Many children will also experience severe reflux issues and may require regular medical suction procedures.

Epigenetics 
"The role of ATRX as a regulator of heterochromatin dynamics raises the possibility that mutations in ATRX may lead to downstream transcriptional effects across the complex of genes or repetitive regions involved in the global context of the disorder, in addition to explaining phenotypical differences in these patients. For example, ATRX mutations affect the expression of alpha-globin gene cluster, causing alpha-thalassemia." ATRX interacts with the transcription co-factor DAXX and the alpha-globin gene cluster. Together they are all responsible for depositing the histone H3.3 at telomeric and pericentromeric regions. They are also responsible for regulating gene expression at these regions. ATRX is characterized by hypo- and hypermethylated regions. It's important to recognize that having a mutation in the ATRX gene does not necessarily guarantee that the patient has ATR-X syndrome. However, it is common within ATR-X patients to have global hypermethylation of usually unmethylated regions, like CpG islands and promoters. Several of the genes that undergo methylation changes are responsible for biosynthetic, metabolic, and methylation processes, and 42.5% of these genes are present in the telomeric and pericentromeric regions. A couple of these genes include: PRDM9 and 2-BHMT2. PRDM9 encodes for a histone H3 lysine-4 trimethyltransferase, which is a known target for ATRX, and 2-BHMT2 encodes for betaine-homocysteine methyltransferase, which catalyzes the methylation of homocysteine.

ATR association can be separated into two groups. ATR-16 syndrome patients have a 1-2Mb deletion on the top of the chromosome 16 p-arm and are associated with a Mendelian inheritance of a-thalassemia. ATR-X syndrome patients have no deletion in chromosome 16, a-thalassemia is rare, and this syndrome is consistent with X-linked recessive inheritance. However, both groups have similar phenotypes. The phenotypes resulting from ATR-X are due to skewed x-inactivation. When X-inactivation occurs randomly, half of the cells in the carrier female would contain the abnormality. When X-inactivation is skewed, more than 50% of one X chromosome are becoming inactive, and if that X-chromosome is passed to a male, they will have a higher percent of heterochromatin. The ATR-X locus spans the control center Xist, which regulates X-inactivation. When there is a XH2 mutation in the ATR-X locus, this indicates Xist to inactivate the chromosome increasing the amount of heterochromatin in males.

Epigenetics is also present among transcriptional regulators. ATR-X is caused by XH2 mutations in the region Xq13.3, and XH2 belongs to the subgroup SNF2. This group is important for regulating the transcription of the alpha genes.

Diagnosis

If ATR-X is suspected based on symptoms, diagnosis can be done via Genome testing. If the results are conclusive with Atr-x syndrome, female members of the same family will often be asked to partake in genome testing to see if anyone else in the family may possess this gene.

Notes

References

Further reading
  GeneReviews/NCBI/NIH/UW entry on Alpha-Thalassemia X-Linked Mental Retardation Syndrome; ATRX Syndrome; Alpha Thalassemia/Mental Retardation, X-Linked; XLMR-Hypotonic Face Syndrome
  OMIM entries on Alpha-Thalassemia X-Linked Mental Retardation Syndrome

External links 

Genetic diseases and disorders
Syndromes