ALBANY — Gov. David Paterson accepted the resignation of his embattled top aide on Friday, after a week of escalating criticism over his failure to pay $300,000 in taxes over a five-year period when he was clinically depressed.

Chief of Staff Charles O’Byrne’s own lawyers appeared to derail his attempt to hold on to his job when they said Wednesday that he suffered from “nonfiler syndrome,” a condition they said was common to professionals. But mental health experts and IRS officials said they never heard of it.

“Members of an elected official’s staff should never distract from the work of the principal who they are privileged to serve,” O’Byrne wrote in a letter to Paterson. “It is clear to me that my personal history has become a distraction to the work of your administration.”

Paterson wrote O’Byrne that he accepts the resignation, effective Friday, with regret.

“I would like to express my gratitude to you for your service in the state Senate and for your service to my administration and for your hard work and dedication in serving the people of New York,” Paterson wrote. “I wish you well in your next endeavor.”

O’Byrne, who has ties to the Kennedy family, has said clinical depression kept him from paying taxes from 2001 to 2005, before he took the job titled secretary to the governor.

O’Byrne’s problems were first made public in the New York Post on Saturday and O’Byrne has been fighting against mounting pressure to keep his $178,500-a-year job since.

Paterson administration officials did not respond to requests for comment.

O’Byrne, an openly gay, former Jesuit priest who officiated at the wedding of John F. Kennedy Jr. and counseled the Kennedy family three years later after he died in a plane crash, was the top aide to Paterson. He was responsible for mapping out policy and politics as Paterson rose from the near powerless Democratic minority in the Senate to lieutenant governor and then governor after Democrat Eliot Spitzer resigned in March amid a prostitution scandal.

O’Byrne’s resignation is a blow to an administration that has fought one crisis after another, beginning with Spitzer’s resignation after just 14 months, much of which was spent in gridlock after fights with the Republican-led Senate.

Since then, Paterson, with O’Byrne, took the extraordinary step of getting the Legislature to agree to cut Spitzer’s last budget, cut 10 percent of spending in the executive branch and warned of dire fiscal problems months before Wall Street’s meltdown. Paterson has planned a second emergency economic session for November in which he’ll try to get the Legislature to cut deeper to help fill a $2 billion deficit.

“Everyone has an obligation to pay their taxes,” said Senate Republican leader Dean Skelos of Long Island. “No one likes to do it, but it is the law and when someone does not comply with the law there are consequences.

“By removing his Chief of Staff Charles O’Byrne, Governor Paterson took appropriate action today to show that no one, even those serving at the highest levels of government, is above the law,” Skelos said.

Skelos also said questions remain about “exactly what the governor knew about O’Byrne’s failure to pay his taxes, and why he chose to do nothing about the matter until it became public this week.”

O’Byrne also hadn’t included the debt in his ethics disclosure statements and could have face fines for the omission. Paterson said O’Byrne informed him of the debt and the depression in 2004 and in 2007. The governor also released a two-year-old letter in which O’Byrne noted the debt and illness. Paterson said state police had found the tax debt didn’t compromise O’Byrne as chief of staff.

O’Byrne’s doctor confirmed he was treated for depression.

This week, Paterson announced that about 60 percent of the 167 workers in the executive chamber, including O’Byrne, didn’t have background reviews concluded.

Dan Weiller, spokesman for the Assembly’s Democratic majority, declined comment.

The question was whether O’Byrne, who often acted as Paterson’s enforcer and harder edge in negotiations, could continue in the critical role. Among O’Byrne’s duties, for example, was negotiating with Indian tribes to get them to start paying hundreds of millions of dollars in state sales tax on cigarettes, gasoline and other sales. The tribes have long opposed that as an infraction on their sovereignty.

O’Byrne’s official title was secretary to the governor, but his duties included those of chief of staff.

Paterson appointed veteran political staffer and adviser Bill Cunningham as acting secretary to the governor. Cunningham has advised governors Hugh Carey and Mario Cuomo and Mayor Michael Bloomberg.

The governor also appointed Deputy Secretary for Labor and Financial Regulation Charlotte Hitchcock as chief of staff and director of financial regulation. She recently was a negotiator for the state in talks with the Federal Reserve to save American International Group Inc. and thousands of jobs when AIG faced dissolution in September, until it received a federal loan.

O’Byrne will assist in a two-week transition.